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The effects of methylphenidate (MPH), atomoxetine (ATMX), and/or physical exercise (EX) on orienting behavior and social interaction were examined in spontaneously hypertensive rats (SHRs), a commonly used animal model of attention-deficit/hyperactivity disorder (ADHD). During the orienting procedure, rats received repeated presentations of a nonreinforced visual stimulus. As observed previously, orienting behavior (rearing up on the hind legs) habituated across trials in normo-active control rats (Wistars) but not in SHRs, suggesting that SHRs have difficulty ignoring irrelevant behavioral stimuli. Treatment with MPH (0.125 mg/kg), ATMX (0.125 mg/kg), or EX (3 weeks of access to a running wheel), alone or in combination, reduced rearing behavior in SHRs to the level observed in the Wistar control group. Similarly, drug treatment and/or EX reduced the number of social interactions exhibited by SHRs, while having no effects on locomotor activity. It is important to note that EX was just as effective as MPH or ATMX in reducing orienting behavior and social interaction. In contrast to the SHRs, neither MPH nor ATMX affected orienting or social behavior in Wistar rats. Together, these findings support the growing literature that EX may be useful as an adjunctive or replacement therapy in ADHD.

We have previously shown that nicotine enhances learning in a negative occasion setting task in which rats are trained to distinguish between two different trial types. During reinforced trials, a target stimulus (a tone) is presented and immediately followed by food reward. On nonreinforced trials, a feature stimulus (a light) is presented prior to the tone and indicates the absence of reward following presentation of the tone. The goal of the present study was to identify the behavioral mechanism through which nicotine affects this form of learning, and to determine which subtype(s) of nicotinic acetylcholine receptors mediate the effects of nicotine. Consistent with our prior findings, nicotine administration enhanced the ability of rats to discriminate between the two trial types. Nicotine enhanced the magnitude of the discrimination by decreasing responding to the tone on nonreinforced trials. Nicotine-treated rats also learned the discrimination in fewer sessions than control rats. A significant new finding was that nicotine also increased the orienting response to the light, suggesting that nicotine may enhance learning the serial feature negative discrimination by increasing attention to the visual feature. In addition, we found that RJR-2403, a selective α4β2 nicotinic receptor agonist, also enhanced discrimination. However, RJR-2403 did not affect responding on nonreinforced trials, nor did RJR-2403 affect orienting to the light. Together these data indicate that nicotine may enhance discrimination by enhancing tone-reward associability through α4β2 nicotinic receptors and by enhancing attention to the light through non-α4β2 receptor subtypes., ((PsycINFO Database Record (c) 2010 APA, all rights reserved).)

The effects of voluntary physical exercise on attentional function and social behavior were examined in male and female spontaneously hypertensive rats (SHR), a commonly used animal model of attention-deficit/hyperactivity disorder (ADHD). Rats in the exercise groups had free access to a running wheel for 2 weeks and then all rats received nonreinforced presentations of a visual stimulus (light) during the 1st training session, followed by daily sessions in which the light was paired with food. Nonexercising male and female SHR rats exhibited more unconditioned orienting behavior than Wistar-Kyoto rats. SHRs also exhibited impaired conditioning when the light was paired with food. Exercise reduced orienting in female SHRs but not in male SHRs. In the social interaction task, nonexercising male and female SHRs interacted more with an unfamiliar rat than Wistar-Kyoto rats. Exercise reduced the number of social interactions in female SHRs but not male SHRs. There were no differences in general locomotor activity observed between the nonexercising and exercising SHRs. These data indicate that exercise may preferentially benefit female SHRs, and has implications for using exercise as an intervention for ADHD and for understanding sex differences in the effects of exercise on behavior., (Copyright (c) 2009 APA, all rights reserved.)

The posterior parietal cortex (PPC) of rats has most recently been defined based on patterns of thalamic and cortical connectivity. The anatomical characteristics of this area suggest that it may be homologous to the PPC of primates and contribute to similar functions. This review summarizes evidence for and against a role for the rat PPC in attention and working memory and evaluates how the function of the rat PPC compares to that of primates on these dimensions. Theories of how the rat PPC contributes to behavior are presented, including the notion that PPC may serve as an interface between attention and learning. Finally, several avenues for future research are considered.

Changes in how well a conditioned stimulus (CS) predicts future events can alter the amount of attention paid to that cue. For example, the unexpected violation of a previously established relationship between a CS and another stimulus can increase attentional processing and subsequent conditioning to that cue [J.M. Pearce & G. Hall (1980)Psych. Rev., 106, 532-552]. Previous lesion studies have implicated the central nucleus of the amygdala (CN) and basal forebrain corticopetal cholinergic system in mediating surprise-induced changes in attention. Here, expression of the immediate-early gene c-fos was used to determine which cortical targets of the basal forebrain cholinergic system are activated during an increase in attentional processing. Consistent with previous studies, increased Fos expression was observed in the posterior parietal cortex (PPC) when a visual stimulus no longer reliably predicted occurrence of a tone. Similar results were observed in the secondary auditory cortex; however, there were no significant changes in Fos expression in other auditory or visual cortices or in other cortical association areas that have been implicated in attentional function (frontal, cingulate or retrosplenial cortex). These findings support the notion that the PPC is the primary cortical component of a neural system mediating incremental changes in attention. In addition, an increase in Fos-positive cells was detected in the substantia innominata/nucleus basalis and the CN at the time of surprise. An opposite pattern of results was observed in the basal lateral nucleus of the amygdala, providing evidence for different stimulus-processing mechanisms in regions of the amygdala.

This study assessed basic learning and attention abilities in Wistar-Kyoto hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hind legs), and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning, but not extinction, was impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as in learning stimulus-reward relationships., ((c) 2005 APA, all rights reserved.)

The authors used an associative learning paradigm to assess the effects of perirhinal or postrhinal damage on attentional orienting. Control rats and rats with lesions of either the perirhinal or postrhinal cortex initially displayed high levels of orienting behavior (rearing) to presentations of a light cue. Continued nonreinforced presentations resulted in normal habituation of the response. In addition, orienting reemerged in control rats, indicating increased attentional processing of the cue. This conditioned orienting did not reemerge in rats with either perirhinal or postrhinal lesions, providing direct evidence that the rat perirhinal and postrhinal cortices each play a role in attention. These results are consistent with an emerging view that some structures within the medial temporal lobe have nonmnemonic functions., (Copyright 2004 APA.)

ABSTRACT Although both genetic and non-genetic factors are known to contribute to the occurrence of Attention-Deficit Hyperactivity/Disorder (ADHD), little is known about how they impact specific symptoms. We used a cross-fostering approach with an established animal model of ADHD, the Spontaneously Hypertensive Rat strain (SHR), to test the influence of genotype and maternal behavior on ADHD-related behaviors. SHRs and their normo-active genetic relative, Wistar Kyoto rats (WKY), were cross-fostered to an unfamiliar dam of either the same or different strain. Behavioral testing took place when the rats reached adulthood. Locomotor hyperactivity was completely dependent on the strain of the offspring. In contrast, social behavior was primarily determined by the strain of the mother, while attentional orienting behavior was influenced by both the strain of the offspring and the strain of the dam. Anxiety-related behavior was influenced by an interaction between offspring and dam strain. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 57: 226-236, 2015. [ABSTRACT FROM AUTHOR]

This study determined the duration of exercise and amount of methylphenidate that is needed to affect attentional function and social behavior in spontaneously hypertensive rats (SHR), a commonly used animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Attention was assessed by measuring the orienting response to repeated presentations of a nonreinforced visual cue. Social behavior was examined by allowing rats to freely explore a large arena containing an unfamiliar conspecific rat. Consistent with their hyper-responsive phenotype, nonexercising SHRs exhibited a high level of orienting behavior and little habituation, as well as hyper-social behavior compared with normo-active rats. Exercise or methylphenidate decreased orienting behavior and social behavior in a dose-dependent fashion. In addition, we found an additive effect of combining doses of exercise and methylphenidate that alone were ineffective in altering behavior. These data indicate that physical exercise and methylphenidate can reduce hyper-responsiveness to irrelevant stimuli and reduce hyper-social behavior in SHR. Moreover, subthreshold doses of methylphenidate can be used in combination with moderate amounts of exercise to reduce distractibility, supporting the notion that exercise may be useful as an adjunctive or replacement therapy in ADHD. [ABSTRACT FROM AUTHOR]

The posterior parietal cortex (PPC) is a component of a major cortico-hippocampal circuit that is involved in relational learning, yet the specific contribution of PPC to hippocampal-dependent learning is unresolved. To address this, two experiments were carried out to test the effects of PPC damage on tasks that involve forming associations between multiple sensory stimuli. In Experiment 1, sham or electrolytic lesions of the PPC were made before rats were tested on a three-phase sensory preconditioning task. During the first phase, half of the training trials consisted of pairings of an auditory stimulus followed by a light. During the other trials, a second auditory stimulus was presented alone. In the next phase of training, the same light was paired with food, but no auditory stimuli were presented. During the final phase of the procedure both auditory stimuli were presented in the absence of reinforcement during a single test session. As is typically observed during the test session, control rats exhibited greater conditioned responding to the auditory cue that was previously paired with light compared to the unpaired cue. In contrast, PPC-lesioned rats responded equally to both auditory cues. In Experiment 2, PPC-lesioned and control rats were trained in a compound feature negative discrimination task consisting of reinforced presentations of a tone-alone and non-reinforced simultaneous presentations of a light-tone compound stimulus. Control rats but not rats with damage to the PPC successfully learned the discrimination. Collectively, these results support the idea that the PPC contributes to relational learning involving multimodal sensory stimuli, perhaps by regulating the attentional processing of conditioned stimuli [ABSTRACT FROM AUTHOR]

The dorsolateral prefrontal cortex (PFC) and posterior parietal cortex (PPC) are two parts of a broader brain network involved in the control of cognitive functions such as working-memory, spatial attention, and decision-making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the PFC to influence memory performance, attention allocation, and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the PFC and PPC, and their underlying mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Kynurenic acid (KYNA) is a tryptophan metabolite synthesized and released by glia and recently shown to be a non-competitive antagonist of α7 nicotinic acetylcholine receptors at physiologically relevant concentrations, and NMDA receptors at higher concentrations. KYNA concentration is elevated in individuals with schizophrenia and those with Alzheimer''s disease, two populations exhibiting cholinergic-related cognitive impairments. The present study investigated the effects of elevated KYNA concentration on conditioned stimulus processing in rats. For the first 2 days of the experiment, a subset of rats received intracerebroventricular infusions of either KYNA (0.1μM) or vehicle and were either returned to the home cage or received non-reinforced presentations of a visual stimulus. All rats subsequently received presentations of the same visual stimulus followed by food reward during a 6-day training phase. In vehicle-treated rats, pre-exposure to the visual stimulus reduced orienting behaviour to the light (standing on the hind legs and orienting towards the visual stimulus) when it was later reinforced (i.e., conditioned orienting). In contrast, pre-exposure to the visual cue or 2 days of KYNA pretreatment reduced conditioned orienting behaviour. Finally, the reduction of orienting in KYNA-treated rats following pre-exposure was not as robust as in vehicle-treated rats. These results suggest that elevated KYNA levels can alter specific aspects of attentional processing of environmental stimuli and are discussed in terms of the potential contribution of KYNA to cognitive function and dysfunction. [Copyright &y& Elsevier]

The central nucleus (CN) of the amygdala and basal forebrain cholinergic projections to the posterior parietal cortex (PPC) are involved in regulating changes in attentional processing of conditioned stimuli. In a previous study, lesions of the CN produced a deficit in conditioned orienting behavior (rearing on the hind legs) when a visual stimulus was paired with food. Unconditioned orienting (rearing to nonreinforced presentations of the stimulus) and conditioned food cup behavior were unaffected. The present study examined the contribution of the PPC to attentional orienting behavior. Damage to the PPC did not affect orienting behavior but produced deficits in food cup behavior. These findings help define the specific contributions of the PPC to attentional processing and associative learning. [ABSTRACT FROM AUTHOR]

Prior research has established that stimulating nicotinic acetylcholine receptors can facilitate learning and memory. However, most studies have focused on learning to emit a particular behavior, while little is known about the effects of nicotine on learning to withhold a behavioral response. The present study consisted of a dose response analysis of the effects of nicotine on negative occasion setting, a form of learned inhibition. In this paradigm, rats received one type of training trial in which presentation of a tone by itself was followed immediately by food reward. During the other type of trials, the tone was preceded by presentation of a light and no food was delivered after the tone. Rats gradually learned to approach the cup in anticipation of receiving food reward during presentations of the tone alone, but withheld that behavior when the tone was preceded by the light. Nicotine (0.35 mg/kg) facilitated negative occasion setting by reducing the number of sessions needed to learn the discrimination between trial types and by reducing the rate of responding on non-reinforced trials. Nicotine also increased the orienting response to the light, suggesting that nicotine may have affected the ability to withhold food cup behavior on non-reinforced trials by increasing attention to the light. In contrast to the effects of nicotine, rats treated with mecamylamine (0.125, 0.5, or 2 mg/kg) needed more training sessions to discriminate between reinforced and non-reinforced trials compared to saline-treated rats. The findings indicate that nicotinic acetylcholine receptors may be active during negative occasion setting and that nicotine can potentiate learned inhibition. [ABSTRACT FROM AUTHOR]

Spontaneously hypertensive rats (SHRs), a commonly used animal model of attention-deficit/ hyperactivity disorder, exhibit little habituation of the orienting response to repeated presentations of a nonreinforced visual stimulus. However, SHRs that have access to a running wheel for 5, 10, or 21 days exhibit robust habituation that is indistinguishable from normo-active rats. Two days of exercise, in comparison, is not sufficient to affect habituation. Here we tested the hypothesis that the effect of exercise on orienting behavior in SHRs is mediated by changes in noradrenergic function. In Experiment 1, we found that 5, 10, or 21 days of access to a running wheel, but not 2 days, significantly reduced levels of the norepinephrine transporter in medial prefrontal cortex. In Experiment 2, we tested for a causal relationship between changes in noradrenergic function and orienting behavior by blocking noradrenergic receptors during exercise. Rats that received propranolol (beta adrenergic/noradrenergic receptor blocker) during 10 days of exercise failed to exhibit an exercise-induced reduction in orienting behavior. The results inform a growing literature regarding the effects of exercise on behavior and the potential use of exercise as a treatment for mental disorders. [ABSTRACT FROM AUTHOR]

Abstract: Kynurenic acid is a tryptophan metabolite that is synthesized and released in the brain by astrocytes and acts as an antagonist of nicotinic acetylcholine receptors and N-methyl-d-aspartate glutamate receptors, both of which are critically involved in cognition as well as neural plasticity and brain development. The concentration of kynurenic acid is increased in the brains of persons with schizophrenia and this increase has been implicated in the cognitive and social impairments associated with the disease. In addition, growing evidence suggests that the increase in kynurenic acid may begin early in life. For example, exposure to influenza A virus during development results in a transient increase in kynurenic acid concentration that could disrupt normal brain development and lead to cognitive deficits later in life. Changes in kynurenic acid may thus provide a link between developmental exposure to viruses and the increased risk of subsequently developing schizophrenia. To test this, we mimicked the effects of influenza A exposure by treating rats with kynurenine, the precursor of kynurenic acid, on postnatal days 7–10. We observed a transient increase in both kynurenic acid and quinolinic acid during treatment. When rats were subsequently behaviorally tested as adults, those previously treated with kynurenine exhibited decreased social behavior and locomotor activity. In contrast, attentional function and fear conditioning were not affected. Together with other recent findings, these data have several implications for understanding how viral-induced changes in tryptophan metabolism during development may contribute to schizophrenia-related symptoms later in life. [Copyright &y& Elsevier]