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Introduction Psychogenic polydipsia, a diagnosis of exclusion, is prevalent among patients with psychiatric disorders. Polydipsia has been associated with catatonia without clear causation or directionality. We describe two cases where polydipsia was a sign of catatonia in the form of stereotypy, represented by abnormally frequent motor behavior. Case 1 A 56-year-old male with a history of bipolar I disorder and obsessive-compulsive disorder presented with paranoid delusions, agitation, poor sleep, self-inflicted injury, and hyponatremia related to polydipsia. Symptoms, including polydipsia, rapidly improved with lorazepam. Due to medication nonadherence, two other similar hospitalizations occurred over the next month, each presenting with polydipsia-related hyponatremia as well as other catatonia symptoms. In each of the three episodes of concurrent catatonia and polydipsia, lorazepam as part of the treatment regimen quickly resolved both the psychiatric and metabolic symptoms. Case 2 A 76-year-old female with a history of bipolar I disorder presented with intrusive speech, impulsive behavior, and decreased sleep, alongside hyponatremia related to polydipsia. She also displayed several catatonic symptoms and was treated with lorazepam and paliperidone. Increasing paliperidone dose worsened the catatonia, polydipsia, and hyponatremia while increasing lorazepam resulted in improvement in these symptoms. Discussion Our patients presented with episodic polydipsia and hyponatremia concurrent with catatonia symptoms. Polydipsia in both cases is a repetitive motor behavior, likely representing a catatonic stereotypy. Our cases illustrate psychogenic polydipsia can sometimes be framed as a catatonic stereotypy, and therefore lorazepam emerges as an option for treatment.

Concerning the matter of depression, its full understanding pushes the envelope beyond clinical psychology and moves the subject further into the areas of Neuropsychopharmacology and Neuromolecular Imaging (NMI). Here, we studied, with the BRODERICK PROBE® acute and chronic stress-induced depression via the hypothalamic–pituitary–adrenal (HPA) axis. The “axis” is responsible for the emission of glucocorticoids during sympathetic nervous system activation. Negative feedback systems within areas of the hippocampus (HPC) and prefrontal cortex (PFC) prevent excessive amounts of glucocorticoids in the neurochemical environment and regulate the HPA axis production of these hormones. In depression, whether or not stress-induced, an increased concentration of glucocorticoids is present. In fact, when released by psychological or physical insult, glucocorticoids are accompanied by cytokines. The purpose of this work is to neuroimage a cytokine storm in the brain as it relates to COVID-19 SARS-CoV-2 patients. The advanced sensor nanobiotechnology, BRODERICK PROBE® transduced a small, protein cytokine, interleukin 1 alpha (IL-1α) to hippocampal Cornu Ammonis (CA-1) in two groups of animal subjects who are walking during neurotransmitter signaling. One genetically normal group was devoid of comorbidity to depression and indeed was also bred without viruses. The other genetic group was bred genetically depressed having platelet storage pool deficiency of the neurotransmitter, serotonin (5-HT); this group presented with Chediak-Higashi Syndrome and are Fawn-Hooded. Microdosing the pro-inflammatory IL-1α showed inherent neuroprotection of the hippocampal cytokine storm during real-time video tracking in Cornu Ammonis neurons in both nondepressed and depressed freely moving and walking subjects. The depressed subjects showed that the cytokine-induced storm began earlier than in nondepressed subjects while walking was increased in addition to enhanced stereotypy. Longer term studies in the same freely moving, walking subjects showed that the nondepressed were adapted to this cytokine brainstorm according to reliable sensor signaling signatures whereas the depressed subjects remained depressed. Thus, at the same time that we watched the brain immune derived cytokine storm directly coming to us online from HPC (CA-1) neurons, we monitored these motor skills with infrared photocell beams. Stereotypic grooming, nasopharyngeal systems were carefully assessed. These skills are important as they are related to respiratory SARS-CoV-2 insults and trauma. We watched online as the feared “hippocampal cytokine storm” was imaged in the depressed subject while immune T cell ratio CD4/CD8 was reversed. Tracking cytokine neuroinflammation transduced to HPC CA-1 neurons directly online while the subject is walking enables direct extrapolation to immune brain dysfunction in SARS-CoV-2 virus (Covid 19) patient data.

Communication is the foundation for mating behavior and social behavior. It involves a signal that is produced by a sending animal and received by another animal that interprets the signal. Senders (or signalers) and receivers co-evolve in the communication process. Evolution refines both the sender's ability to send a meaningful signal and the recipient's ability to perceive and understand the signal. Signals used in communication evolve following the basic principles of co-option, ritualization, stereotypy, and redundancy. Modes, or channels, such as sight, sound, or touch are used in animal communication. Each mode has advantages and disadvantages, depending on the environmental conditions and the signaling and receiving capacities of the species. Signals are often honest, but sometimes deceitful signaling is advantageous, which is especially important in mate choice. Once broadcast, signals become public information, available both to the intended recipient and to other animals, which might take advantage of the signal. Noise interferes with signaling and influences the evolution of communication by causing selection to favor sensory mechanisms that filter noise or behavior that avoids noise. The potential for human-caused noise to disrupt animal communication is a major conservation concern. Interspecific signaling occurs when a signal has evolved to influence the behavior of other species. Communication is the keystone in the arch of behavior from the individual to its participation in behavioral interactions with other animals.

Tourette syndrome (TS) is a neurodevelopmental syndrome characterized by motor and vocal tics, as well as by sensory abnormalities; it is frequently comorbid with other neuropsychiatric conditions such as obsessive-compulsive disorder (OCD). The construction of valid animal models of such conditions presents particular challenges. All three normal domains in which validity is assessed are problematic: face validity because the symptomatology is complex and difficult to define in an animal; predictive validity because available pharmacological interventions are of limited efficacy and specificity; and construct validity because our understanding of the pathophysiology of these complex disorders remains rudimentary. Despite these challenges, a variety of animal models of these conditions have been described. Models of TS have focused on dysregulation of dopamine and of inhibitory transmission within the cortico-basal ganglia circuitry. Models of OCD have focused on the same circuitry, as well as on serotonergic modulation and on a variety of behavioral manipulations. No established models have yet been convincingly shown to fully recapitulate the pathophysiology of these prevalent diseases; but several have cast important insight on underlying neurobiological processes and are likely to continue to be informative going forward.

Dyskinesias are a common consequence of dopaminergic therapy in patients with Parkinson's disease. Little is known about the influence of cellular replacement strategies upon drug-induced dyskinesias. In the current study, we employed parkinsonian rats to test whether the distribution of dopamine neuron grafts could differentially alter striatal circuitry and levodopa-induced dyskinesias. Specifically, we compared behavioral and neurochemical consequences of dopamine reinnervation restricted to a focal region of the striatum to innervation encompassing the majority of the striatum by distributing the same number of cells into single locus or multiple locations. Both the single-site and widespread grafts reduced pregraft dyskinesias and normalized FosB/ΔFosB in the dorsal two-thirds of the lateral striatum. However, single-site DA graft recipients developed a robust, novel forelimb-facial stereotypy and upregulated FosB/ΔFosB expression in the ventrolateral striatum, an area associated with movements of tongue and forelimbs. The onset of forelimb-facial stereotypy correlated with measures of increased graft function.

Obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts and repetitive motor actions. Hyposerotonergic signalling in the cortico-striatal circuitry is believed to be central to the pathology of OCD, while many patients only respond to chronic treatment with high dose selective serotonin (5HT) reuptake inhibitors (SSRIs). Confined deer mice spontaneously develop two forms of stereotypy, namely vertical jumping and pattern running. The purpose of this investigation was to reappraise these behaviours and strengthen the validity of deer mouse stereotypy as an animal model of OCD within a framework of three study questions: (1) can the time spent executing stereotypical behaviours be employed as a measure of extent of stereotypy, (2) does deer mouse stereotypy only respond to chronic, but not sub-chronic treatment with a high-dose SSRI, and (3) is deer mouse stereotypy associated with altered cortico-striatal 5HT transporter (SERT) binding? The current study demonstrates that treatment naïve high stereotypical (HS) deer mice spend significantly more time executing stereotypical behaviours while significantly less time is spent indulging in stereotypy following chronic, but not sub-chronic, treatment with escitalopram. Furthermore, HS deer mice present with a significant decrease in striatal SERT density compared to non-stereotypical (NS) controls. Building on previous validation studies, we conclude that deer mouse stereotypy is a valid naturalistic animal model of OCD with robust face, construct and predictive validity. http://www.journals.elsevier.com/behavioural-brain-research/

The most prevalent sub-group of abnormal repetitive behaviors among captive animals is that of stereotypies. Previous studies have demonstrated some resemblance between stereotypy in captive animals and in humans, including the involvement of neurological malfunctions that lead to the expression of stereotypies. This malfunction can be evaluated through the use of neuropsychological tasks that assess perseveration as implying a failure of the basal ganglia (BG) to operate properly. Other studies, in contrast, have suggested that stereotypies are the product of neurologically intact individuals reacting to the abnormal nature of their surroundings, and are possibly characterized by an adaptive feature that enables the subject to cope with such adversity. Employing neuropsychological tests and also measuring the levels of fecal corticoids in captive rhesus macaques, we tested the hypothesis that stereotypies are related both to brain pathology and to a coping mechanism with stress, resembling accounts by autistic individuals exhibiting basal ganglia malfunction, and who report a sense of relief when performing stereotypies. Self-directed and fine-motor stereotypies exhibited by the monkeys were positively correlated with perseveration, suggesting BG malfunction; while self-directed stereotypies were also negatively correlated with an increase in fecal corticoids following a stress challenge, suggesting a related coping mechanism. We therefore suggest that not all repetitive, unvarying, and apparently functionless behaviors should be regarded as one homogeneous group of stereotypic behaviors; and that, reflecting reports from autistic individuals, self-directed stereotypies in captive rhesus monkeys are related both to brain pathology, and to an adaptive mechanism that allows those that express them to better cope with acute stressors.

Nonhuman primates in captivity sometimes show a range of abnormal behaviors. These behaviors are reviewed, focusing on ‘isolation syndrome’ pathologies that result from early social deprivation, including self-sucking, clasping, bizarre postures, and repetitive, stereotyped motor acts. Primates that are reared with inadequate amounts of early social experience develop to be socially inept, with affiliative, agonistic, and reproductive behaviors seriously disturbed. They may also show self-aggression, which may be injurious. Normal primates housed in individual cages may also develop abnormal behaviors including stereotypies, which can be reduced and sometimes eliminated through environmental enrichment.

Publisher Summary Children and adults with autism spectrum disorders (ASD) are at much greater risk of showing a wide range of challenging behavior (CB) than typically developing people. This chapter reviews various aspects of assessment of CB. These include the reasons for assessment, assessment of topographies, and assessment of function and its implications for treatment. Common problems including aggression, stereotypy, and eating problems in people with ASD are also reviewed. Of most immediate concern are extra-personal maladaptive behaviors, such as aggression and tantrums, because of their negative and sometimes severe consequences for the person and those around them. Intra-personal maladaptive behaviors may also be significant as they may be stigmatizing and may interfere with learning and the expression of adaptive behavior. There are many psychometric measures to assess CB topographies. They can be quick and efficient in the early stages of assessing CB, in screening larger populations, and in periodic screening of individuals, such as during admission to services and annual evaluations. The CB topographies can be readily assessed with screening questionnaires, but these questionnaires are limited in that they do not provide all the information necessary to design an effective intervention plan. Information regarding the establishing operations (Eos), discriminative stimuli, functionally equivalent adaptive and maladaptive behaviors, and contingencies maintaining the CB greatly improve the design of an effective treatment plan. Despite the efficacy of this approach to treatment of CB in people with ASD, certain problems, such as pica, remain more difficult to treat. Additionally, more research involving the dissemination of this technology to routine care providers and practitioners is needed.

Publisher Summary This chapter reviews the epidemiology of stereotypy, considering the prevalence, demographics, and forms associated with these behaviors. Stereotypic movements are repetitive behaviors varying little in topography; that do not appear to serve a meaningful purpose. Stereotypy has been presumed to serve self-stimulatory or perceptual consequence functions. They occur for a variety of reasons, but all are a function of some type of reinforcement produced directly by the response (nonsocial reinforcement) or by changing the behavior of others. The chapter discusses how stereotypy is conceptualized and the emerging functional perspective that is being used. A review of functional assessment approaches is used to identify the causes of stereotypy. The chapter describes various approaches used in a functional behavioral assessment (FBA) to identify specific functions that a person's stereotypy may serve and also focuses on the function-based interventions derived from functional assessments of stereotype.

Publisher Summary Dystonia is defined as a syndrome of sustained muscle contractions causing twisting or repetitive movements or abnormal postures. It is classified as focal, segmental, multifocal, generalized or hemi-dystonia according to the distribution of the symptoms. Primary or idiopathic dystonia represents a condition with no known cause, and usually lacks clinical signs other than dystonic muscle contractions. Some are found clearly genetic, and rarely accompany Parkinsonism and hyperreflexia (DOPA-responsive dystonia or DRD). Dystonia may be secondary to focal lesions, other neurological illnesses, or prolonged use of major tranquilizers or related drugs (secondary dystonia). Although widely used, the above definition does not fully represent the salient clinical features of this disorder, and some additional points deserve mention. Writer's cramp is a focal dystonia of the hand, which typically affects only writing at its onset. This task-specificity may also be seen in other forms of dystonia. Abnormal muscle contractions involve the same set of muscles in the same way such that the movements are stereotyped; patients with cervical dystonia—for example, always present involuntary head turning to a fixed direction. This distinguishes dystonia from other involuntary movements such as seen in chorea or athetosis, which lack stereotypy.

Infantile spasms represent a unique age-specific epileptic syndrome that is often associated with a focal or diffuse encephalopathy and can result in severe neurodevelopmental delay and retardation. The behavioral and electroencephalogram (EEG) phenotype of infantile spasms is similar, despite its association with multiple neurological disease states. The stereotypy suggests that the spasms originate from a highly age-specific hyperexcitable network. Treatment strategies for infantile spasms remain largely empirical due to the lack of understanding of the underlying neurochemistry and circuitry. This chapter reviews experimental evidence for the presence of unique developmental factors that appear to promote hyperexcitability in the immature brain and that may play a role in the generation of infantile spasms. In addition, this chapter evaluates the potential interplay between an associated developmental encephalopathy and enhanced neuronal hyperexcitability in infantile spasms.

Phenotypes were assessed topographically in mice lacking functional D2 dopamine receptors [‘knockouts’], using an ethologically based approach to assess all behaviours in the natural repertoire. D2-null mice evidenced an ethogram characterised initially by modest reductions in locomotion and shifts in rearing topographies. Subsequently, topographies of behaviour habituated similarly for wildtypes and ‘knockouts’. Following challenge with the D2-like agonist RU 24213, both inhibition of rearing at a lower dose and induction of stereotyped sniffing and ponderous locomotion at higher doses were essentially absent in D2-null mice. Following challenge with the D1-like agonist A 68930, vacuous chewing was released in D2-null mice. This topographical approach to phenotypic characterisation implicates: (i) the D2 receptor in these D2-like agonist effects and in oppositional D1-like: D2-like interactions; and (ii) the operation of material compensatory processes consequent to the developmental absence of D2 receptors which are able to maintain ethological function under tonic, ‘naturalistic’ conditions but not under ‘phasic’ challenge. Fil: Clifford, Jeremiah J.. Royal College of Surgeons; Irlanda. Tralee General Hospital; Irlanda Fil: Kinsella, Anthony. Dublin Institute of Technology; Irlanda Fil: Tighe, Orna. Royal College of Surgeons; Irlanda Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Grandy, David K.. Oregon Health Science University; Estados Unidos Fil: Low, Malcolm J.. Oregon Health Science University; Estados Unidos Fil: Croke, David T.. Royal College of Surgeons; Irlanda Fil: Waddington, John L.. Royal College of Surgeons; Irlanda

Publisher Summary This chapter reviews the evidence for genetic factors contributing to variability in the functional, neurochemical, and neuroanatomical organization of the basal ganglia. Most of the citations reviewed in the chapter involve comparisons amongst inbred strains of mice or rats. The purpose of many inbred strain studies is not only to establish the existence of genetic differences, but also to test hypotheses about relationships between traits, for example, apomorphine-induced stereotypy and D2 receptor density. Strain similarities on multiple traits suggest a common genetic influence. The chapter reviews the phenotypes (for example, receptor density, drug responses, dopamine neuron number), which are quite complex. When such complex phenotypes are characterized in a large panel of inbred stains or in genetically segregating population, the phenotypic values are usually continuously distributed. To explain this observation, quantitative genetic theory argues that multiple genes, each with a modest effect, combine to produce the phenotypic variance.

This chapter examines facial reflexes and the ontogeny of facial displays. To begin with, the facial reflexes are crucial to any evolutionary account of human facial displays. Normal adult facial physiology includes various reflexes that are generally considered innate and immutable and are characterized by few synapses. These reflexes are generally protective, although some are now mostly vestigial, such as the Hering-Breuer (dive) reflex, which slows the heart when the face is cooled. The facial reflexes are usually divided into three kinds: (1) superficial reflexes, (2) visceral reflexes, and (3) myotatic reflexes. Both the normal and, in infancy, the pathological facial reflexes act to facilitate more complex activities. These actions are very complex and their effects are too broad to be considered typical reflexes, but their stereotypy and inertia make them reflex-like. Many theorists are interested generally in the relations between facial actions and those of the autonomic nervous system (ANS). Adults shape the child's developing displays, and the raw material shaped by this parental pedagogy is the repertoire of preexisting facial reflexes. Subsequently, children may develop mature displays by direct imitation of caretakers who model and prompt for appropriate displays; this mechanism is entirely independent of the form and function of the facial reflexes. Three cases of reflexes and their arguably emancipated counterparts in adult human displays can be proposed: (1) tickling and amusement displays, (2) startle and surprise displays, and (3) gagging and revulsion displays.

The 1940s and 1950s saw the emergence of two trends that furthered the study of facial behavior: the first was the investigation of Woodworth and Schlosberg of the dimensionality of emotions through factor-analytical studies of photographed faces and the second was the emphasis of ethologists such as Lorenz and Tinbergen on the innateness and almost comical stereotypy of some nonhuman consumatory and social behavior. Early ethology's documenting of instinctual, reflex-like behavior gave new impetus to evolutionary views of human behavior, and some ethologists ambitiously extended their findings to human societies. The synthetic view of evolution by natural selection was first articulated by Theodosius Dobzhansky in the landmark Genetics and the Origin of Species . In the case of facial displays, many features of facial expressivity could be under genetic control; the control may be either mono- or polygenic. Also, genetic control of a trait implies that its origins are in natural selection and doesn't imply current evolution through natural selection. Thereafter, an array of investigative strategies can be brought into play to help determine the extent of a trait's genetic control or the extent and trend of its evolution. Finally, any learning or mimicry must rely on a genetic complement. Displays may be learned or not learned, to a greater or lesser extent, in one form but not another, depending upon one's innate competences.

Publisher Summary This chapter examines the effect of L-dopa and carbidopa on behavioral recovery produced by ventral mesencephalic grafts in rats. Fetal dopamine grafts may have a role in reducing the severity of apomorphine-induced stereotypy, which may be related to changes in the numbers of D-1 and/or D-2 receptors in the striatum. The fact that L-dopa treatment alone or in combination with fetal grafts causes an increase in stereotypy, whereas fetal grafts alone cause a decrease, may have relevance to the drug induced dyskinesias observed in patients with Parkinson's disease. In 6-hydroxydopamine (6-OHDA) lesioned rats, treatment with L-dopa and carbidopa is not detrimental to the survival and function of ventral mesencephalic fetal grafts as revealed by reversal of (+)-amphetamine- and apomorphine-induced rotation. In addition, fetal grafts alone may prevent the increase in apomorphine-induced stereotypy known to develop both with L-dopa treatment and in rats with unilateral nigro-striatal lesions.

Publisher Summary This chapter discusses the activation of dopaminergic neurons by sulpiride. Sulpiride is an atypical neuroleptic because within a given dose range, it has various effects—it produces catalepsy only at toxic doses, it does not block apomorphine induced stereotypy, and in particular, it fails to block dopamine (DA) sensitive adenylate cyclase (AC) both in vitro and in vivo. The chapter presents the effects of sulpiride on the electrical activity of single identified DA neurons in the rat substantia nigra (SN) to clarify whether the increased dopaminergic activity elicited by neuroleptics was mediated by the blockade of D1 or D2 receptors. The present results show that intravenously injected (-)-sulpiride, but not the (+) enantiomer, increases the firing rate of DA cells in the SN and antagonizes apomorphine-induced inhibition of firing. Moreover, the local microiontophoretic application of (-)-sulpiride fails to interfere with the basal activity of DA cells in the SN, but prevents the DA-induced inhibition in these neurons.

Publisher Summary This chapter discusses antagonism to dopaminergic stereotypy and convulsant and hypertensive effects by 2-amino-4-methylpyridine (2-AMP). 2-AMP resembles morphine in some pharmacological properties but differs from the opiate in others. Thus, the implantation of morphine into the lateral thalamus of rats causes stereotyped behavior, but the deposition of 2-AMP into this region is ineffective. The thalamic application of apomorphine also evokes stereotypy. Thus, this effect is because of direct or indirect activation of dopamine receptors; on this mechanism, 2-AMP has no influence. On the other hand, systemic morphine suppresses stereotyped behavior, caused by injection of apomorphine or by thalamic implantation of morphine, and a similar inhibition is produced by systemic 2-AMP. The antagonistic effect of either morphine or 2-AMP against stereotypy is abolished by the pretreatment of the rats with p-chlorophenylalanine and may, therefore, be ascribed to the activation of an inhibitory serotonergic mechanism. Large i.v. doses of 2-AMP produce convulsions in wake rabbits but are rather ineffective in cats under pentobarbitone anesthesia or in spinal or pithed cats. Whenever seizures appear, they are accompanied by a sharp and prolonged rise of blood pressure in marked contrast to the morphine-induced hypotension.

Publisher Summary This chapter discusses a study to examine the participation of cholinergic mechanisms in the memory effects of central nervous system (CNS) stimulants. The experiments were carried out on albino rats. Training and memory testing on an active avoidance task with punishment reinforcement were performed in a maze or in a shuttle-box. Only one training session was carried out. Retention tests were conducted 24 h and 7 days after the end of the training session. The drugs were administered i.p. only once either before or immediately after learning. The results obtained from maze- and shuttle-box-trained rats were unambiguous. It was found that CNS stimulants with a different mechanism of action as caffeine, theophylline, strychnine, amphetamine, centedrine (methylphenidate), centrophenoxine (meclophenoxate), Leuzea carthamoides extract, etc. administered in single doses producing no seizures or stereotypy, before or immediately after learning, facilitated long-term memory. The stimulants administered 30 min or later after training did not significantly influence retention. This led to the belief that the stimulants facilitated acquisition, but their main effect is on early memory consolidation.

We studied apomorphine-induced stereotyped behavior (A-ISB), which depends in part on striatal dopaminergic mechanisms, in rats as an animal model of tardive dyskinesia. To examine the involvement of cholinergic synapses in A-ISB, we rated the intensity of stereotypy in rats given both apomorphine and a direct or indirect cholinergic agonist. We found that certain, but not other, cholinergic drugs were successful in blocking A-ISB.

Publisher Summary This chapter provides an overview of various animal models of stereotypy. It examines some neurobiological evidence relevant to theoretical explanations of pathological stereotypies and highlights connections between the pathological stereotypies seen in mentally retarded persons and repetitive movement patterns seen elsewhere in nature. The stereotypies observed in human infants involve rhythmic movement patterns, such as kicking, waving, rocking, head banging, and nonnutritive sucking. Despite evidence for central control, large individual differences in the amount of stereotypy have been observed among normal infants. A fuller understanding requires that stereotypies be conceptualized as biobehavioral processes in which neurochemical and neurophysiological events are in dynamic transaction with environmental and behavioral events. Stereotyped behavior exhibited by mentally retarded people is not discontinuous activities; it represents the logical expression of events along a number of biological continua. The chapter presents specific evidence, which shows that stereotypy is linked to traceable neurochemical events, particularly the activity of the neurotransmitter dopamine.

We have studied the time course of haloperidol-induced alterations in striatal DA receptor site characteristics in guinea pigs. After 3 weeks of haloperidol treatment, behavioral supersensitivity for apomorphine stereotypy developed, and striatal DA receptor site and concentration increased. Supersensitivity of DA receptors persisted at 3 weeks post-treatment, behavioral and binding assays reavealed a return to control values. These findings suggest that haloperidol-induced supersensitivity of DA receptor sites can be reversible.

Publisher Summary This chapter discusses the experimental synthesis of behavior. Learning involves the formation of representations that are considerably more abstract than connections between sensory inputs and particular muscle twitches. The units of behavior may be defined functionally in terms of their effects on the environment, and generalizations should be sought relating environmental events such as reinforcement to the occurrences of these functional units. The chapter describes the effects of pretraining variations on the experiments conducted on the behavior of individuals. The pretraining confounds two variables of potential significance. It includes reinforcement and involves a contingency that produces a high degree of stereotypy. The four experiments discussed in the chapter show that a history of reinforcement contingent on particular successful patterns of behavior can have negative transfer effects in later tasks that were substantially different from the pretraining task. The chapter describes the negative effects of rewards. If the application of instructional techniques involving reinforcement contingencies becomes sufficiently widespread, the problematic category of intelligent variation may disappear as a characteristic of human behavior in need of explanation.

Publisher Summary Isofloxythepin is a new oral neuroleptic drug with long-acting action. This chapter discusses a study for the development of supersensitive state on dopaminergic receptors after the acute administration of neuroleptic drug isofloxythepin. The effect of isofloxythepin on dopaminergic system in rats was found biphasic. In short intervals (24 and 48 h after the administration), striatal HVA and DOPAC were increased and apomorphine stereotypy was counteracted. On the contrary, in long intervals (4–6 days), both DA metabolites were decreased significantly below the control values and apomorphine stereotypy was enhanced. The influence of isofloxythepin on prolactin secretion, its interaction with apomorphine on striatal HVA, and repeated administration of isofloxythepin were compared in short and long intervals. The stereospecifity of isofloxythepin action was also demonstrated. The observed delayed reversion of dopaminergic transmission after isofloxythepin might be explained by the development of supersensitivity state on dopaminergic receptors.

We present evidence that five week daily administration to rats of either phenylethylamine, d-amphetamine, or cocaine produce qualitatively and quantitatively similar stereotyped behavior. Haloperidol and pimozide block all drug-induced stereotypy, whereas clozapine antagonizes only phenylethylamine stereotypy. In membrane receptor binding studies using 3H-dopamine, we found that no chronic pretreatment significantly affected striatal dopamine receptor affinity, whereas cocaine and d-amphetamine, but not phenylethylamine, increased the density of striatal dopamine receptors. These results are discussed in light of formulating a representative animal model for schizophrenia.

Publisher Summary This chapter presents a review that aims to bring together what is known of the physiology of ecdysis with what is known of the behavior of ecdysing insects and shows how one is integrated with the other. Ecdysial behavior is probably largely programmed within the CNS, but once initiated the details of its performance may be more or less influenced by sensory feedback according to the species, and which part of the behavior is being considered. The exceptional stereotypy of the abdominal movements involved in the preeclosion and eclosion behavior of H. cecropia and the confinement of eclosion to a narrow, temporal “gate” by a circadian clock in the brain are key factors that led to the discovery of the role of the eclosion hormone in initiating eclosion behavior. The chapter provides evidence that silkmoth eclosion behavior is initiated directly by eclosion hormone. H. cecropia and A. pernyi emerge from the pupal cuticle only at a particular time of day, during relatively narrow gates determined by a circadian clock. If the pharate adults are removed from their pupal cases during the few hours before the normal eclosion gate, then they continue to show predominantly pupal behavior. In the case of A .pernyi , this is particularly striking, the peeled moth showing very little spontaneous motor activity at all. However, at the time of the normal eclosion gate, the moths go through a pantomime emergence, despite having been free of the pupal case for several hours.

Rats were treated for 6 months with butyrophenone, phenothiazine or thioxanthene neuroleptics. Stereotypy responses to 0.15 mg/kg apomorphine remained antagonised and striata showed similar increases in 3H-spiperone binding, suggesting enduring functional blockade and masked ‘supersensitivity’ of DA2 receptors. However, spontaneous perioral movements and ‘vacuous chewing’ and hyperlocomotion to apomorphine and SK & F 38393, a putative DA1 agonist, distinguished the phenothiazines and thioxanthenes from the butyrophenone. Either DA1 and DA2 receptors can be dissociated functionally or behaviours previously equated with DAergic processes may be independant of such processes.

6-Hydroxydopamine (6-OHDA) lesions of the nucleus accumbens septi (NAS) reduced spontaneous activity for 7 days. At 11 days after lesion, the locomotor response to amphetamine (AMPH) (0.5, 1.0, 2.5 and 5.5 mg/kg) was significantly decreased, whereas the measures of stereotypy were unaltered. Behavioral augmentation resulted from repeated AMPH administration in sham but not lesioned animals. The results suggest that this augmentation may be at least partly mediated by alterations in nonstriatal dopamine (DA) systems.

An analysis was made of the interaction between naloxone (NX) and striatal dopaminergic (DA) mechanisms in an attempt to elucidate the complex action of this drug on behavior. In doses ranging from 0.20-0.80 mg/kg, NX inhibited the stereotyped behavior induced by the directly acting DA agonist apomorphine (AISB), in a dose-dependent manner. NX (0.40 mg/kg) also produced a sigmoidal inhibition of the stereotypy induced by successive low doses of apomorphine (0.10-0.25 mg/kg). Since the effect of NX on behavior has been shown to be species dependent, an identical study was also undertaken in the guinea pig. Though NX exerted similar effects on AISB in both the rat and guinea pig and the stereotypy curves plotted for both species were of nearly identical configuration, low doses of apomorphine produced considerably more stereotypy in the guinea pig than did identical doses in the rat. The concomitant administration of the indirect DA agonist d-amphet-amine (0.50-5.0 mg/kg) resulted in an effect opposite to that seen with NX and apomorphine. NX potentiated amphetamine induced stereotypy (AmISB) with the amphetamine + NX curve significantly above and virtually parallel to the amphetamine + saline curve. To test the hypothesis that these effects were the result of an action exerted by NX on the release of striatal DA, the effect of NX on AISB was assessed in the presence and absence of drugs that inhibit DA release non-specifically (MPT) and specifically (-hydroxybutyric acid). Pretreatment with either drug significantly reversed the inhibitory effect of NX on AISB relative to saline pretreated animals. This was consistant with previous observations that drugs enhancing striatal DA levels also inhibit AISB in a dose-dependent manner, and potentiate AmISB. These results are also in agreement with our recent findings that NX (10−6 M) can significantly enhance the release of 3H-DA stimulated by d-amphet amine (10−6 M) in rat striatal slices in vitro . NX appears to enhance striatal DA levels only if the nigrostriatal pathway is in a state of arousal (e.g. by amphetamine). This effect is probably not mediated by a direct action of NX on presynaptic DA receptors, but rather appears to be produced indirectly by an action on presynaptic opioid receptors localized on striatal DA nerve terminals.