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The currently dominant neuro-cognitive model of Attention Deficit Hyperactivity Disorder (AD/HD) presents the condition as executive dysfunction (EDF) underpinned by disturbances in the fronto-dorsal striatal circuit and associated dopaminergic branches (e.g. meso-cortical). In contrast, motivationally-based accounts focus on altered reward processes and implicate fronto-ventral striatal reward circuits and those meso-limbic branches that terminate in the ventral striatum especially the nucleus accumbens. One such account, delay aversion (DEL), presents AD/HD as a motivational style-characterised by attempts to escape or avoid delay-arising from fundamental disturbances in these reward centres. While traditionally regarded as competing, EDF and DEL models have recently been presented as complimentary accounts of two psycho-patho-physiological subtypes of AD/HD with different developmental pathways, underpinned by different cortico-striatal circuits and modulated by different branches of the dopamine system. In the current paper we describe the development of this model in more detail. We elaborate on the neuro-circuitry possibly underpinning these two pathways and explore their developmental significance within a neuro-ecological framework.

Infection of the central nervous system with human immunodeficiency virus type-1 (HIV) is associated with cognitive impairments that range from mild cognitive and motor difficulties to dementia. Structural neuroimaging abnormalities are also common in HIV-infected patients both with and without cognitive disturbances. The most common abnormalities include high signal intensities in the white matter and atrophy. Research over the past 12 years has helped define the relationship between these neuroimaging abnormalities and the manifestation of cognitive disturbance in HIV. In the present paper, we provide a synopsis of these studies and report the current state of the literature. Our review revealed that atrophy of the caudate nucleus is most consistently associated with cognitive impairment in HIV. The current literature does not support a strong relationship between cortical atrophy or white matter abnormalities and cognitive dysfunction in this population, though methodological issues may have influenced the results. Suggestions for study design and new research directions are provided.

Studying the behavioral phenotypes of transgenic and gene knockout mice is a powerful means to better understand the pathophysiology of neuropsychiatric disorders and ultimately improve their treatment. This paper provides an overview of the methods and findings of studies that have tested for anxiety-related behavioral phenotypes in gene mutant mice. In the context of improving the side effect burden of benzodiazepines, gene targeting has been valuable for dissociating the functional roles (i.e., anxiolytic, sedative, amnestic) of individual GABA(A) receptor subunits. Supporting the link between abnormalities in CRH function and anxiety, CRH overexpressing transgenic mice and CRH-R2 receptor knockout mutants have displayed significantly increased anxiety-like behavior, while CRH-R1 receptor knockout mice have shown an anxiolytic-like phenotype. Consistent with an important role for the serotonergic system in anxiety, 5-HT1(A) receptor deficient mice have consistently exhibited heightened anxiety-like behavior, while the evidence from 5-HT1(B) and 5-HT2(C) deficient mice remains somewhat equivocal. Mutant mice lacking either of the monoamine degrading enzymes, MAOA or COMT, have shown a number of behavioral and neurological effects, including alterations in anxiety-like behavior. With enhanced spatial and temporal control over gene mutations, in combination with an improved battery of behavioral tests, gene mutant mice will provide an increasingly valuable tool for understanding the neural substrates of anxiety.

Akathisia is a complex neurobehavioural side effect of neuroleptics and some other drugs which is characterised by subjective report and objective manifestations of restlessness. Its pathophysiology is poorly understood and there are many limitations to its investigation in humans. This paper reviews the various attempts that have been made in modelling acute akathisia in animals. Homologous as well as isomorphic models have been attempted, but most models are partial as they reproduce either the subjective or the objective features of the syndrome. None of the available models has been fully validated. Neuroleptic-induced defecation in the rat, even though constrained by a lack of symptom similarity and thereby face validity, has been most studied as a model of subjective akathisia. Rat models of restlessness, in particular those involving the use of serotonergic drugs or lesions of the ventral tegmentum or medial prefrontal cortex, are interesting partial models that should be further investigated. Neuroleptic-induced akathisia is observed in primates and has been modelled in dogs, and these should be studied further for their validation. It is also necessary to consider the subtypes of akathisia in the attempts to develop these models.

The neurotransmitter histamine is contained within neurons clustered in the tuberomammillary nuclei of the hypothalamus. These cells give rise to widespread projections extending through the basal forebrain to the cerebral cortex, as well as to the thalamus and pontomesencephalic tegmentum. These morphological features suggest that the histaminergic system acts as a regulatory center for whole-brain activity. Indeed, this amine is involved in the regulation of numerous physiological functions and behaviors, including learning and memory, as indicated by extensive research reviewed in this paper. Histamine effects on cognition might be explained by the modulation of the cholinergic system. However, interactions of histamine with any transmitter system, and/or a putative intrinsic procognitive role cannot be excluded. Furthermore, although experimental evidence indicates that attention-deficit hyperactivity disorder symptoms arise from impaired dopaminergic and noradrenergic transmission, recent research suggests that histamine is also involved. The possible relevance of histamine in disorders such as age-related memory deficits, Alzheimer's disease and attention-deficit hyperactivity disorder is worth of consideration, and awaits validation with clinical trials that will prove the beneficial effects of histaminergic drugs in the treatment of these diseases.

Sensitivity to noxious stimulation is not invariant; rather, it is modulated by discrete pain inhibitory and facilitatory circuits. This paper reviews the neural circuits for pain facilitation, describes the conditions governing their environmental activation, and examines their role in an animal's behavioral repertoire. Mechanisms for pain facilitation are contrasted at both the neural and behavioral level with mechanisms for pain inhibition. In addition, the involvement of mechanisms for pain facilitation in morphine analgesic tolerance is discussed, and the implications of this involvement for accounts of the role of associative processes in analgesic tolerance are highlighted.

The use of reaction time has a great tradition in the field of human information processing research. In animal research the use of reaction time test paradigms is mainly limited to two research fields: the role of the striatum in movement initiation; and aging. It was discussed that reaction time responding can be regarded as "single behavior", this term was used to indicate that only one behavioral category is measured, allowing a better analysis of brain-behavior relationships. Reaction time studies investigating the role of the striatum in motor functions revealed that the initiation of a behavioral response is dependent on the interaction of different neurotransmitters (viz. dopamine, glutamate, GABA). Studies in which lesions were made in different brain structures suggested that motor initiation is dependent on defined brain structures (e.g. medialldorsal striatum, prefrontal cortex). It was concluded that the use of reaction time measures can indeed be a powerful tool in studying brain-behavior relationships. However, there are some methodological constraints with respect to the assessment of reaction time in rats, as was tried to exemplify by the experiments described in the present paper. On the one hand one should try to control for behavioral characteristics of rats that may affect the validity of the parameter reaction time. On the other hand, the mean value of reaction time should be in the range of what has been reported in man. Although these criteria were not always met in several studies, it was concluded that reaction time can be validly assessed in rats. Finally, it was discussed that the use of reaction time may go beyond studies that investigate the role of the basal ganglia in motor output. Since response latency is a direct measure of information processing this parameter may provide insight into basic elements of cognition. Based on the significance of reaction times in human studies the use of this dependent variable in rats may provide a fruitful approach in studying brain-behavior relationships in cognitive functions.

The present paper reviews literature data on the role of the non-specific central nervous system response mechanisms on the therapeutic effects of relatively weak external stimulations used in clinical practice. The factors affecting the stimulation efficiency and increased sensitiveness of living things to extra-low-frequency periodic stimulations (in the range of from less than 1 Hz to tens of Hz) are discussed. Among the factors determining such effects, the non-specific response mechanisms of the nervous system, the resonance phenomena in different organism systems, and the interaction of external stimulation with endogenous rhythmic processes are analyzed. Most attention is given to endogenous rhythms of the electrical brain activity reflected in the EEG rhythms. A high resolution EEG processing approach that is used to reveal the intrinsic oscillators in the individual EEG spectrum is described. Synchronization of sensory stimulation parameters with the frequencies of intrinsic EEG oscillators is supposed to be an appropriate way to enhance the therapeutic effects of various sensory stimulation treatments. Specific methods for utilizing resonance therapy via sensory stimulation with intrinsic EEG frequencies, and for automatic modulation of stimulation parameters by endogenous organism rhythms are delineated; some preliminary results are described.

SAINSBURY R. S. Hippocampal theta: a sensory inhibition theory of function. NEUROSCI BIOBEHAV REV 22(2), 237–241, 1998.—The most prominent electrical signal which can be recorded from the hippocampus is called theta rhythm. Over the past 30 years there have been numerous attempts to relate this waveform to behavior. Theta has been associated with arousal, learning memory, attention, and most recently motor movement. While the relationship between one type of theta and certain kinds of movement is well established, a second type of theta shows no such relationship. In the present paper it is argued that the most parsimonious hypothesis relating theta to behavior is not the motor programming theory but a sensory-inhibition model. In this model theta is regarded as representative of general inhibition of systems not being used during motor behavior or alert immobility.

KIRK, I.J. Frequency modulation of hippocampal theta by the supramammillary nucleus, and other hypothalamo-hippocampal interactions: mechanisms and functional implications. NEUROSCI BIOBEHAV REV 22 (2), 291–302, 1998.—In this paper it is argued that theta-range hippocampal EEG activity, and in particular the specific frequency at which it occurs, is critical to hippocampal function. Results of the reviewed studies suggest that in particular circumstances (in the urethane anaesthetized animal and possibly during particular behavioral states), the frequency of hippocampal theta is primarily determined in the supramammillary nucleus (SuM). Rhythmic theta-frequency neuronal activity in the SuM is relayed to, and determines the frequency of theta activity in, the septum (and hence the hippocampus). It is also suggested that in general (e.g. freely moving, as opposed to anaesthetized animals, and in all but some specific behavioral states), other ascending pathways and mechanisms in addition to those from SuM are probably also involved in the modulation of theta frequency. The posterior hypothalamic nucleus (PH) probably acts in synergy with the SuM, but it is principally involved in the release and amplitude modulation of theta. Although descending input from the septo–hippocampal system to PH and SuM is not required for theta-related neuronal activity in these structures, we provide evidence for descending, rate-limiting influences from the septo–hippocampal system to both PH and SuM during theta. These descending systems are likely involved in the suppression of theta during non-theta (i.e. sharp-wave) hippocampal EEG. In contrast to the SuM and PH, theta-related neuronal activity in the medial mammillary nucleus (MM) is dependent on theta-frequency activity in, and descending from, the septo–hippocampal system. The MM it is argued, is involved in relaying theta-frequency activity around the limbic circuitry. A role for this re-entrant process is suggested.

This paper proposes a three phase "model" of the neuropharmacological processes responsible for the seizures and neuropathology produced by nerve agent intoxication. Initiation and early expression of the seizures are cholinergic phenomenon; anticholinergics readily terminate seizures at this stage and no neuropathology is evident. However, if not checked, a transition phase occurs during which the neuronal excitation of the seizure per se perturbs other neurotransmitter systems: excitatory amino acid (EAA) levels increase reinforcing the seizure activity; control with anticholinergics becomes less effective; mild neuropathology is occasionally observed. With prolonged epileptiform activity the seizure enters a predominantly non-cholinergic phase: it becomes refractory to some anticholinergics; benzodiazepines and N-methyl-D-aspartate (NMDA) antagonists remain effective as anticonvulsants, but require anticholinergic co-administration; mild neuropathology is evident in multiple brain regions. Excessive influx of calcium due to repeated seizure-induced depolarization and prolonged stimulation of NMDA receptors is proposed as the ultimate cause of neuropathology. The model and data indicate that rapid and aggressive management of seizures is essential to prevent neuropathology from nerve agent exposure.

While aging has been associated with changes in the period and amplitude of circadian rhythms, little is known about how aging influences the response of the circadian clock to environmental stimuli. In this paper, we report on recent studies designed to determine the effects of advanced age on the response of the circadian clock to both photic and nonphotic stimuli in old hamsters (e.g., over 16 mo of age). Among the most pronounced age-related changes in the circadian rhythm of locomotor activity are: (a) alterations in the phase-angle of entrainment to the light-dark cycle; (b) an increase in the magnitude of phase shifts induced by pulses of light presented at specific circadian times; and (c) a loss of responsiveness to the phase shifting or entraining effects of stimuli which induce an acute increase of activity. Depletion of brain monoamine levels in young animals can induce changes in the responsiveness of the circadian clock to environmental stimuli which are similar to those which occur spontaneously in old animals, suggesting that aging alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal SCN tissue. Determining the physiological basis for age related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian function can be restored, should lead to new insight into the functioning of the circadian clock and may lead to new approaches for normalizing disturbed circadian rhythms.

This paper presents an hypothesis regarding the functions of striatal dopaminergic and glutamatergic neurotransmission. It is suggested that the principal functional role of dopaminergic neurotransmission is to regulate the efficacy of cortico-striatal and cortico-accumbens neurotransmission. Increased activity at dopamine-mediated synapses is suggested to interact with neurotransmission at adjacent cortically derived glutamate-mediated synapses, facilitating communication from the cerebral cortex, and thereby causing behavioral stimulation. Decreased activity at dopaminergic synapses, as produced by neuroleptic drugs, causes changes in the activation of cortically derived synapses in the corpus striatum and nucleus accumbens which result in behavioral sedation and decreased activity. This hypothesis suggests that activity at dopaminergic synapses produces behavioral effects only insofar as these changes modulate cortico-striatal (or cortico-accumbens) activity, and further, that the manifestations of activity in cortico-striatal systems are modulated by activity at dopaminergic synapses. It is further suggested that when neuroleptics are administered chronically, adjustments in the efficacy of cortico-striatal neurotransmission are responsible for the antipsychotic effect of neuroleptic drugs.

Sweeteners are widely used in the food and pharmaceutical industry. The purpose of this paper is to review our current knowledge of sweet taste from chemical, biochemical, electrophysiological, psychophysical, and psychological points of view. The most common sweetners likely to be used in food and pharmaceuticals will be examined in detail. First, the chemical structures of sweet compounds including saccharides, diterpene glycosides, polyols, amino acids, dipeptides, and other nonsugars will be discussed. Second, biochemical approaches to understanding sweetner receptors will be reviewed. Third, electrophysiological and behavioral approaches to understanding sweetner receptors will be discussed. Fourth, psychophysical studies in humans will be shown to be consistent with biochemical and neurophysiological data. In addition, the basic mechanisms of sweet taste revealed by psychophysical studies will be given, including the role of multiple receptor sites, hydrogen bonding, and sodium transport. Finally, the factors that affect preference for sweet taste including the psychological and physiological variables associated with sweet preference will be explored.

Photic stimulation of the human visual system with uniform but intermittent illumination has been recognized for well over a century to give rise to the perception of complex visual patterns and forms. A review of the literature pertaining to these "stroboscopic patterns" is presented, along with a review of theories addressing their origins. The theories range from attributing the patterns to inhomogeneities in the structure of the eye, to the formation of functional domains of neural activity. A novel account of the origins of the patterns is developed in this paper utilizing advances in the neurobiology of information processing and nonlinear dynamics. This view conceptualizes the patterns as examples of "dissipative structures." These dissipative structures are conceived of as self-organizing macrostates of spatio-temporal coherence, widespread among visual cortical neurons. This self-organization is described in terms of nonlinear dynamics, in which sets of attractors emerge within a neural phase space undergoing constant change as the energy contained within successive volleys of stimulation-induced action currents is recursively dissipated by the visual system through cooperative feedback. The trajectories of activity formed by these attractors may reflect the actual form of the perceived patterns themselves and are thought to correspond to some of the reported properties of "linking fields" in the visual cortex.

The present paper reviews recent pharmacological evidence indicating an important role for central monoaminergic neurotransmission in the mediation of lordosis behavior in the female rat. Following the initial observations by Meyerson and his colleagues in the early 1960s, demonstrating an inhibitory serotonergic mechanism, continued studies have identified 5-hydroxytryptamine (5-HT) 5-HT1A receptors to be of particular importance. Stimulation of central 5-HT2 receptors appear to have an opposite role, i.e. facilitating the elicitation of the lordosis response. As regards brain dopaminergic neurotransmission, it appears that brain dopamine (DA) D2 receptors mediate an inhibitory effect on the lordosis behavior, whereas no distinct role has been ascribed to DA D1 receptors. The serotonergic and the dopaminergic mechanisms can be manipulated independently, perhaps indicating the operation of parallel mechanisms. Most of the evidence presented above has been obtained in experiments on ovariectomized female rats primed with subthreshold doses of estrogen. It appears, however, that at least the inhibitory effects mediated by serotonergic neurotransmission are not dependent on the presence of progesterone.

In recent years, the burgeoning disciplines of health psychology and behavioral medicine have renewed interest in the important role that environmental factors can play in the disease process. Nowhere is this concern more well-founded than in the area of cardiovascular disorders, particularly hypertension. Epidemiologists and clinicians have long suspected that stressful life events can be a sufficient trigger for the expression of hypertension in some individuals. To understand better the ways in which these variables interact in the disease process, researchers have tried, with limited success, to produce experimental hypertension in animals by exposing them to stressful environmental paradigms. Additionally, recent investigations using the borderline hypertensive rat (BHR) have demonstrated the important role genetic factors can play in mediating both the behavioral and cardiovascular responses to environmental stressors. The current paper will review these attempts and discuss recent data from experiments using a relatively new animal model that appears to be especially appropriate for the study of environmental-genetic factors in the elaboration of essential hypertension. We will also discuss potential mechanisms by which environmental stress influences arterial pressure and suggest avenues for further inquiry into the stress-disease relationship.

Chronic sequential administration of a variety of mild stressors causes a decrease in responsiveness to rewards in rats, which is reversed by chronic administration of antidepressant drugs. This paper reviews the validity of chronic mild stress-induced anhedonia as an animal model of depression, and the evidence that changes in hedonic responsiveness in this model are mediated by changes in the sensitivity of dopamine D2 receptors in the nucleus accumbens. The review opens with an analysis of the design features of animal models of depression, and ends with a brief account of other animal models of anhedonia.

We have employed the unilateral removal of the vibrissae as a tool to examine ensuing behavioral changes in relation to concomitant changes in the central nervous system. In this paper we review a series of studies showing that unilateral removal of the vibrissae leads to behavioral asymmetries (e.g., in thigmotactic scanning) from which rats recover over time. Time-related to these behavioral changes we found neuronal alterations in striatal afferents, that is, in uncrossed and crossed projections from the substantia nigra and the tuberomammillary nucleus. The involvement of dopaminergic mechanisms was indicated by results showing that dopaminergic agonists can induce asymmetries in thigmotactic scanning and turning; the direction of these asymmetries was also dependent on time after vibrissae removal. Furthermore, it was shown that endogenous preferential use of one vibrissae side in thigmotactic scanning interacts with the expression of spontaneous and drug-induced behavioral asymmetries exhibited after unilateral vibrissae removal. Neurochemical studies indicated that both unilateral vibrissae removal and unilateral perioral stimulation can have lateralized effects on biogenic amines in the brain. Finally, using electrical stimulation of the substantia nigra, evidence was found for a lateralized and bidirectional interaction between basal ganglia and the orofacial systems, indicating an involvement in mechanisms of motivation and particular stimulation. These results are important from several perspectives. One, they indicate functional links between the orofacial systems and the basal ganglia. Two, they raise the possibility that unilateral removal of the vibrissae can serve as a model (a) to investigate the dynamics of recovery of function after CNS insults, in general, and specifically, (b) to study neuronal plasticity in the nigrostriatal and tuberomammillary-striatal pathways, and (c) to investigate the neuropharmacology of catecholamine systems in the brain.

This paper proposes a new theory addressing the neural mechanism of declarative memory consolidation and retrieval. The premise of the theory is that the cortex is responsible for the storage of declarative memory while the medial temporal lobe is responsible for the consolidation and retrieval of declarative memory. The theory suggests that the medial temporal lobe can only accomplish its functions related to memory by hierarchically and cooperatively regulating the descending limbic system, including the hypothalamus, epithalamus, septum, mammillary bodies and the bed nucleus of the stria terminalis. These descending limbic structures, together with the amygdala, further send efferents to the four ascending NA, 5-HT, DA and ACh systems. It is these four ascending extrathalamic regulatory systems that provide the feedback neural pathways to the cortex and regulate the processes of memory consolidation and retrieval in the cortex. Therefore, the coupling of these descending limbic structures to the ascending NA, 5-HT, DA and ACh systems completes the neural circuits responsible for the consolidation and retrieval of new declarative memories. This neural mechanism of declarative memory consolidation and retrieval is universal to all species in higher mammals.

The authors regret the following error in their recent publication. On page 684 they described an experiment on temporal discounting onducted by Green et al. (1994). Here, they incorrectly stated that Green et al. (1994) observed an age-related increase in discount rates, hen in fact Green et al. (1994) found lower discount rates in older adults compared to younger adults and pre-teen. This result is, however, nly partly in line with later findings by Harrison et al. (2002) and Read and Read (2004). As correctly described in this paper, both studies eport decreasing discount rates from young adulthood to middle adulthood, but increasing discount rates from middle adulthood to old dulthood, suggesting a potential U-shaped relationship between age and delay discounting across wider age ranges.

One hypothetical model for a mechanism of drug dependence involves the development of an adaptive process that is initiated to counter the acute effects of the drug. This adaptive process persists after the drug has been cleared from the brain, leaving an opposing reaction unopposed (abstinence signs). From a motivational perspective a particularly attractive hypothesis has been that of opponent process theory (32). Here many reinforcers elicit positive affective and hedonic processes that are opposed by negative affective and hedonic processes. Thus the intense pleasure of the opiate drug "rush" or "high" would be opposed by aversive withdrawal symptoms. The present paper presents neurobiological evidence to support the opponent process concept and suggests neural circuitry that may be involved. The region of the nucleus accumbens in the forebrain of the rat has been shown to be a particularly sensitive substrate not only for the acute reinforcing properties of opiate drugs, but also for the response disruptive effects of opiate antagonists in opiate dependent rats. This region also appears to be particularly sensitive to the aversive stimulus effects of opiate antagonists using a place aversion measure in dependent rats. These results suggest that the region of the nucleus accumbens and its neural circuitry may be an important neural substrate for both the positive and negative motivational aspects of drug dependence.

This paper reviews: the development of benzodiazepine binding-sites and the GABA system; the evidence that prenatal exposure to benzodiazepines can cause malformations; other persisting effects of developmental exposure to benzodiazepines; and the behavioral effects of benzodiazepines (and other relevant drugs) in immature animals. The review concentrates on the rat, since fundamental work in other species is scarce. The data on neurochemical development are found to be generally consistent; however, reports that the enhancement of benzodiazepine binding by GABA varies with age are controversial. The physical development of the rat is disturbed only by extremely high doses of benzodiazepines. The evidence for persisting effects after early exposure to benzodiazepines is impressive at first sight, but in most studies, confounding variables have not been eliminated. Startle and some learning tasks are affected by prenatal diazepam; submissiveness is affected by neonatal lorazepam; social behaviour and convulsions are affected by neonatal CGS 8216. Benzodiazepines inhibit chemically-induced seizures in neonatal rats, but the developmental profile of sensitivity to the convulsants is disputed. Benzodiazepines stimulate motor behavior in the neonatal rat.

The classic “hypothalamocentric” theory of thirst has increasingly been challenged because the effects of hypothalamic lesions are not as behaviorally or anatomically specific as earlier research indicated. Instead, the attention of investigators in the field has increasingly been drawn to the lateral preoptic region and the tissues surrounding the anterior third ventricle. The present paper reviews these developments and proposes that still another diencephalic structure, the subthalamic region known as the zona incerta, may play a major role in the regulation of thirst and water intake.

This paper examines findings on the neuroregulatory effects of nicotine in an effort to formulate a unified hypothesis that can explain the remarkable persistence of smoking behavior. Because nicotine alters the bioavailability of several behaviorally active neuroregulators, including acetylcholine, norepinephrine, dopamine, beta-endorphin, and vasopressin, we propose that nicotine is “used” by smokers to produce temporary improvements in performance or affect. Under this formulation, a potentially large number of exteroceptive and interoceptive cues unrelated to the nicotine-dependence cycle may serve as discriminative stimuli for smoking, over and above smoking to terminate or avoid withdrawal. The rapid action of nicotine, and its diverse neuroregulatory effects, render it particularly effective as a “coping response” to the demands of daily living. Of special interest in this regard is a biphasic pattern of arousal/alertness during smoking followed by calming/tension-reduction after smoking, which may result from cholinergic/catecholaminergic activation followed by cholinergic blockade or betaendorphin release. Apparently smokers can adjust nicotine intake to enhance these effects selectively, which may add considerably to the appeal of smoking.

Four hypotheses have been advanced to explain the relationships between the cholinergic presynaptic afferents, principal ganglionic neurons, and small, intensely fluorescent (SIF) cells in synaptic transmission in the mammalian superior cervical ganglion (SCG). The first hypothesis involves the role of the dopaminergic SIF cell and cyclic AMP in the modulation of ganglionic transmission through the generation of a slow inhibitory postsynaptic potential (s-IPSP). The second concerns the generation of a slow excitatory postsynaptic potential (s-EPSP), and the role of dopamine and cyclic AMP in potentiating it. The third postulates that a presynaptic α-adrenergic receptor is responsible for inhibiting f-EPSP generation. A fourth hypothesis concerns the localization of the β-adrenergic receptor—adenylate cyclase complex in SCG. This paper discusses the evidence for each hypothesis, with special emphasis on species variations in the modulation of ganglionic transmission by catecholamines, adrenergic receptors, and cyclic AMP.

The present paper reviews the effects of stress on noradrenergic receptor function in the brain. Most forms of stress thus far examined have been found to reduce either the magnitude of the cAMP response to stimulation by catecholamines (CAs) and/or the density of beta adrenergic receptors in the brain. These effects (a) generally occur in the cerebral cortex, (b) are more marked after chronic than acute stress, (c) may be the result of excessive release of norepinephrine (NE), ACTH or serotonin (5-HT) and (d) may occur in neurons glia or both. The function of these receptor alterations is not known but is presumed to be related in some manner to adaptation to chronic stress. A review of similar changes occurring in peripheral organs after repeated stress or CA injections reveals that subsensitivity of beta adrenergic receptors can be associated with either decreases or increases in CA-stimulated organ output. The latter findings caution against concluding that there is a decreased postsynaptic noradrenergic function after adaptation to chronic stress. Instead they suggest that it may be more appropriate to view stress-induced receptor subsensitivity as part of a more complex pattern of adaptive changes which includes alterations in the size, number, efficiency and output of CA effector cells.

In this paper we have reviewed the literature on Conditioned Taste Aversion (CTA) with specific attention to the "apparent paradox" in this literature. This paradox refers to the fact that drugs which are self-administered (SA) by animals and are therefore presumed to possess positive reinforcing properties are also endowed with the capacity to induce a CTA. We have argued that the CTA literature contains evidence of the existence of two qualitatively distinct types of CTA, one which is mediated by emetic agents and the other induced by SA drugs. We first provided evidence to support the notion that the traditional explanation of CTA as a function of "drug toxicity" and its resultant gastrointestinal distress does not fit the data on the nature of CTA induced by SA drugs. We proposed instead that "drug shyness" or the novelty of the drug state of these psychoactive SA drugs constitutes a better explanation of the CTA of SA drugs. We provided further evidence suggesting a functional relationship between the positive reinforcing and aversive properties of SA drugs. We have based this contention on a review of the behavioral, physiological and neurochemical data concerning the nature of CTA of SA drugs. The examination of these data reveals that the neural mechanisms underlying both the positive and aversive properties of SA drugs are the same and at the same time different from the neural mechanisms underlying the induction of CTA by emetic agents. Finally, we discussed the relevance of this interaction between the positive and aversive properties of SA drugs in the context of their abuse liability and the control they exert on drug-oriented behavior.

Highlights • We review brain anatomical studies of tinnitus. • We evaluate the “gating mechanism” in light of the evidence from these studies. • We discuss the results and the possible causes of disparity between findings. • Overall, the evidence for structural abnormalities in tinnitus is unconvincing. • We identify methodological concerns and suggest strategies for future research., In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research.

Regular physical activity (PA) offers positive effects on the human body. However, the effects of PA on cognition and in the brain are less clear. In this paper, we narratively review the relationship of PA with cognition and dementia, first from general perspective and then through genetically informed studies on the topic. Then we move on to imaging studies on exercise and brain anatomy first by presenting an overall picture of the topic and then discussing brain imaging studies addressing PA and brain structure in twins in more detailed way. Regarding PA and cognition or dementia, genetically informed studies are uncommon, even though the relationship between PA and cognitive ageing has been extensively studied. It is challenging to find twin pairs discordant for PA and dementia. Concerning brain imaging studies, among PA discordant young adult twin pairs, the more active co-twins showed larger gray matter volumes in striatal, prefrontal, and hippocampal regions and in electrophysiological studies automatic deviance-detection processes differed in brain regions involved with sensorimotor, visual and memory functions.

Research on action understanding in cognitive neuroscience has led to the identification of a wide "action understanding network" mainly encompassing parietal and premotor cortical areas. Within this cortical network mirror neurons are critically involved implementing a neural mechanism according to which, during action understanding, observed actions are reflected in the motor patterns for the same actions of the observer. We suggest that focusing only on cortical areas and processes could be too restrictive to explain important facets of action understanding regarding, for example, the influence of the observer's motor experience, the multiple levels at which an observed action can be understood, and the acquisition of action understanding ability. In this respect, we propose that aside from the cortical action understanding network, sub-cortical processes pivoting on cerebellar and basal ganglia cortical loops could crucially support both the expression and the acquisition of action understanding abilities. Within the paper we will discuss how this extended view can overcome some limitations of the "pure" cortical perspective, supporting new theoretical predictions on the brain mechanisms underlying action understanding that could be tested by future empirical investigations.