The D2-like Dopamine Receptor Agonist Quinpirole Microinjected Into the Ventral Pallidum Dose-Dependently Inhibits the VTA and Induces Place Aversion.

BACKGROUND: The ventral pallidum (VP) is a dopaminoceptive forebrain structure regulating the ventral tegmental area (VTA) dopaminergic population activity. We have recently demonstrated that in the VP, the D2-like dopamine (DA) receptor agonist quinpirole dose dependently facilitates memory consolidation in inhibitory avoidance and spatial learning. According to our hypothesis, quinpirole microinjected into the VP can modulate the VTA DAergic activity and influence motivation and learning processes of rats. METHODS: Quinpirole was microinjected at 3 different doses into the VP of male rats, and controls received vehicle. Single unit recordings were employed to assess VTA DAergic activity. To investigate the possible reinforcing or aversive effect of quinpirole in the VP, the conditioned place preference paradigm was used. RESULTS: Our results showed that intra-VP quinpirole microinjection regulates VTA DAergic neurons according to an inverted U-shaped dose-response curve. The largest dose of quinpirole decreased the population activity and strongly reduced burst activity of the DAergic neurons in the first hour after its application. In contrast, the 2 smaller doses increased DA population activity, but their effect started with a delay 1 hour after their microinjection. The CPP experiments revealed that the largest dose of quinpirole in the VP induced place aversion in the rats. Furthermore, the largest dose of quinpirole induced an acute locomotor activity reduction, while the medium dose led to a long-duration increase in locomotion. CONCLUSIONS: In summary, quinpirole dose dependently regulates VTA DAergic activity as well as the motivation and motor behavior of the rats at the level of the VP.

The role of social support in the dietary behavior of coronary heart patients: an application of the health action process approach.

Dietary behaviour plays a crucial role in both the onset and the management of coronary artery disease (CAD). To develop effective interventions to modify dietary behaviours of patients, it is fundamental to identify and examine the predictive factors that are relevant to healthy dietary behaviour. The Health Action Process Approach provides a useful framework for understanding and predicting the process of health behaviour. The aim of the current study is to clarify the role and effect of received social support in the HAPA model. A longitudinal sample of 117 CAD patients filled out a questionnaire at three time points. Along with HAPA constructs, dietary behaviour was assessed with a food frequency questionnaire. To investigate the longitudinal associations of the constructs, structural equation modelling with latent variables was employed. In the final model, outcome expectancies and pre-action self-efficacy jointly predicted behavioural intention. In the post-intentional phase, social support served as a mediator between intention and action planning. Moreover, coping planning mediated the relationship between action planning and dietary behaviour. These results confirmed the mediator role of social support in the intention-behaviour relationship. This finding suggests that social support can be a crucial component to facilitate healthy dietary behaviour.

Hemokinin-1 mediates anxiolytic and anti-depressant-like actions in mice.

The tachykinin NK1 receptor was suggested to be involved in psychiatric disorders, but its antagonists have failed to be effective as antidepressants in clinical trials. Hemokinin-1 (HK-1), the newest tachykinin, is present in several brain regions and activates the NK1 receptor similarly to substance P (SP), but acts also through other mechanisms. Therefore, we investigated the roles of the Tac4 gene-derived HK-1 in comparison with SP and neurokinin A (NKA) encoded by the Tac1 gene, as well as the NK1 receptor in anxiety and depression-like behaviors in mice. Mice lacking SP/NKA, HK-1 or the NK1 receptor (Tac1-/-, Tac4-/-, Tacr1-/-, respectively) compared to C57Bl/6 wildtypes (WT), and treatment with the NK1 antagonist CP99994 were used in the experiments. Anxiety was evaluated in the light-dark box (LDB) and the elevated plus maze (EPM), locomotor activity in the open field (OFT) tests. Hedonic behavior was assessed in the sucrose preference test (SPT), depression-like behavior in the tail suspension (TST) and forced swim (FST) tests. FST-induced neuronal responsiveness was evaluated with Fos immunohistochemistry in several stress-related brain regions. In the LDB, Tac4-/- mice spent significantly less, while Tacr1-/- and CP99994-treated mice spent significantly more time in the lit compartment. In the EPM only Tac4-/- showed reduced time in the open arms, but no difference was observed in any other groups. In the OFT Tac4-/- mice showed significantly reduced, while Tac1-/- and Tacr1-/- animals increased motility than the WTs, but CP99994 had no effect. NK1-/- consumed markedly more, while Tac4-/- less sucrose solution compared to WTs. In the TST and FST, Tac4-/- mice showed significantly increased immobility. However, depression-like behavior was decreased both in cases of genetic deletion and pharmacological blockade of the NK1 receptor. FST-induced neuronal activation in different nuclei involved in behavioral and neuroendocrine stress responses was significantly reduced in the brain of Tac4 -/- mice. Our results provide the first evidence for an anxiolytic and anti-depressant-like actions of HK-1 through a presently unknown target-mediated mechanism. Identification of its receptor and/or signaling pathways might open new perspectives for anxiolytic and anti-depressant therapies.

[MAM-E17 schizophrenia rat model]. / A MAM-E17 szkizofrénia patkánymodell.

Schizophrenia is a serious neuropsychiatric disorder. Several brain structures, neurotransmitter systems, genetic and environmental risk factors are suspected in the background. Because of its complexity the mechanism of the disorder is not known exactly, so the treatment of patients is unsolved. In the research of schizophrenia application of the rodent models is widespread. In this study one of these models based on the effect of methylazoxymethanol- acetate (MAM) is described, which is a neurodevelopmental, validated rat model. This antimitotic agent is able to evoke a number of schizophrenic symptomes temporarily disrupting the prenatal neurogenesis. The model reproduces numerous histological and neurophysiological changes of the human disorder, moreover it also represents several behavioral and cognitive phenomena resembling those in schizophrenia. A salient advantage of the model is the demonstration of the diachronic feature of the disorder, that is, postpubertal appearance of the positive symptoms. This model provides widespread opportunities for manipulations of the symptoms, so that using it in the future investigations can lead to a better understanding of this disorder.

Receptive field properties of color opponent neurons in the cat lateral geniculate nucleus.

Most nonprimate mammals possess dichromatic ("red-green color blind") color vision based on short-wavelength-sensitive (S) and medium/long-wavelength-sensitive (ML) cone photoreceptor classes. However, the neural pathways carrying signals underlying the primitive "blue-yellow" axis of color vision in nonprimate mammals are largely unexplored. Here, we have characterized a population of color opponent (blue-ON) cells in recordings from the dorsal lateral geniculate nucleus of anesthetized cats. We found five points of similarity to previous descriptions of primate blue-ON cells. First, cat blue-ON cells receive ON-type excitation from S-cones, and OFF-type excitation from ML-cones. We found no blue-OFF cells. Second, the S- and ML-cone-driven receptive field regions of cat blue-ON cells are closely matched in size, consistent with specialization for detecting color contrast. Third, the receptive field center diameter of cat blue-ON cells is approximately three times larger than the center diameter of non-color opponent receptive fields at any eccentricity. Fourth, S- and ML-cones contribute weak surround inhibition to cat blue-ON cells. These data show that blue-ON receptive fields in cats are functionally very similar to blue-ON type receptive fields previously described in macaque and marmoset monkeys. Finally, cat blue-ON cells are found in the same layers as W-cells, which are thought to be homologous to the primate koniocellular system. Based on these data, we suggest that cat blue-ON cells are part of a "blue-yellow" color opponent system that is the evolutionary homolog of the blue-ON division of the koniocellular pathway in primates.

The antipsychotic agent sulpiride microinjected into the ventral pallidum restores positive symptom-like habituation disturbance in MAM-E17 schizophrenia model rats.

Dysfunction of subcortical D2-like dopamine receptors (D2Rs) can lead to positive symptoms of schizophrenia, and their analog, the increased locomotor activity in schizophrenia model MAM-E17 rats. The ventral pallidum (VP) is a limbic structure containing D2Rs. The D2R antagonist sulpiride is a widespread antipsychotic drug, which can alleviate positive symptoms in human patients. However, it is still not known how sulpiride can influence positive symptoms via VP D2Rs. We hypothesize that the microinjection of sulpiride into the VP can normalize hyperactivity in MAM-E17 rats. In addition, recently, we showed that the microinjection of sulpirid into the VP induces place preference in neurotypical rats. Thus, we aimed to test whether intra-VP sulpiride can also have a rewarding effect in MAM-E17 rats. Therefore, open field-based conditioned place preference (CPP) test was applied in neurotypical (SAL-E17) and MAM-E17 schizophrenia model rats to test locomotor activity and the potential locomotor-reducing and rewarding effects of sulpiride. Sulpiride was microinjected bilaterally in three different doses into the VP, and the controls received only vehicle. The results of the present study demonstrated that the increased locomotor activity of the MAM-E17 rats was caused by habituation disturbance. Accordingly, larger doses of sulpiride in the VP reduce the positive symptom-analog habituation disturbance of the MAM-E17 animals. Furthermore, we showed that the largest dose of sulpiride administered into the VP induced CPP in the SAL-E17 animals but not in the MAM-E17 animals. These findings revealed that VP D2Rs play an important role in the formation of positive symptom-like habituation disturbances in MAM-E17 rats.

The role of intraamygdaloid oxytocin in spatial learning and avoidance learning.

The goal of the present study is to investigate the role of intraamygdaloid oxytocin in learning-related mechanisms. Oxytocin is a neuropeptide which is involved in social bonding, trust, emotional responses and various social behaviors. By conducting passive avoidance and Morris water maze tests on male Wistar rats, the role of intraamygdaloid oxytocin in memory performance and learning was investigated. Oxytocin doses of 10 ng and 100 ng were injected into the central nucleus of the amygdala. Our results showed that 10 ng oxytocin significantly reduced the time required to locate the platform during the Morris water maze test while significantly increasing the latency time in the passive avoidance test. However, the 100 ng oxytocin experiment failed to produce a significant effect in either of the tests. Wistar rats pretreated with 20 ng oxytocin receptor antagonist (L-2540) were administered 10 ng of oxytocin into the central nucleus of the amygdala and were also subjected to the aforementioned tests to highlight the role of oxytocin receptors in spatial- and avoidance learning. Results suggest that oxytocin supports memory processing during both the passive avoidance and the Morris water maze tests. Oxytocin antagonists can however block the effects of oxytocin in both tests. The results substantiate that oxytocin uses oxytocin receptors to enhance memory and learning performance.

Antibiotics and probiotics-induced effects on the total fatty acid composition of feces in a rat model.

Fatty acids (FAs) play important roles as membrane components and signal transduction molecules. Changes in short chain FA (SCFA) composition are associated with gut microbiota modifications. However, the effect of bacteria-driven changes on the detailed FA spectrum has not been explored yet. We investigated the effect of antibiotics (ABx) and/or probiotics, in four treatment groups on rat stool FA composition. Principal component analysis indicated that the chromatogram profiles of the treatment groups differ, which was also observed at different time points. Linear mixed effects models showed that in the parameters compared (sampling times, treatments. and their interactions), both the weight percentage and the concentration of FAs were affected by ABx and probiotic administration. This study found that the gut microbiome defines trans and branched saturated FAs, most saturated FAs, and unsaturated FAs with less carbon atoms. These results are among the first ones to demonstrate the restoring effects of a probiotic mixture on a substantial part of the altered total FA spectrum, and also revealed a previously unknown relationship between gut bacteria and a larger group of FAs. These findings suggest that intestinal bacteria produce not only SCFAs but also other FAs that may affect the host's physiological processes.

Intraamygdaloid Oxytocin Increases Time Spent on Social Interaction in Valproate-Induced Autism Animal Model.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder that affects about 1.5% of children worldwide. One of the core symptoms is impaired social interaction. Since proper treatment has not been found yet, an investigation of the exact pathophysiology of autism is essential. The valproate (VPA)-induced rat model can be an appropriate way to study autism. Oxytocin (OT) may amend some symptoms of ASD since it plays a key role in developing social relationships. In the present study, we investigated the effect of the intraamygdaloid OT on sham and intrauterine VPA-treated rats' social interaction using Crawley's social interaction test. Bilateral guide cannulae were implanted above the central nucleus of the amygdala (CeA), and intraamygdaloid microinjections were carried out before the test. Our results show that male Wistar rats prenatally exposed to VPA spent significantly less time on social interaction. Bilateral OT microinjection increased the time spent in the social zone; it also reached the level of sham-control animals. OT receptor antagonist blocked this effect of the OT but in itself did not significantly influence the behavior of the rats. Based on our results, we can establish that intraamygdaloid OT has significantly increased time spent on social interaction in the VPA-induced autism model, and its effect is receptor-specific.

Novel Noninvasive Paraclinical Study Method for Investigation of Liver Diseases.

Based on a prior university patent, the authors developed a novel type of bioimpedance-based test method to noninvasively detect nonalcoholic fatty liver disease (NAFLD). The development of a new potential NAFLD diagnostic procedure may help to understand the underlying mechanisms between NAFLD and severe liver diseases with a painless and easy-to-use paraclinical examination method, including the additional function to detect even the earlier stages of liver disease. The aim of this study is to present new results and the experiences gathered in relation to NAFLD progress during animal model and human clinical trials.

Role of received social support in the physical activity of coronary heart patients: The Health Action Process Approach.

Physical activity (PA) plays a crucial role in the management of coronary artery disease (CAD). The Health Action Process Approach provides a useful framework for understanding and predicting the process of health behaviors. The aim of the current study was to unveil the role of received social support in the HAPA model, concerning the physical activity of CAD patients. A longitudinal sample of 117 CAD patients filled out a questionnaire during three measurement points (baseline, 2 months, and 6 months later). The constructs within the model were measured by the previously validated HAPA scales. PA was assessed with four items, which were also included in the HAPA questionnaire. To test the direct and indirect associations between the variables, structural equation modeling with latent variables was employed. Received social support was proven to have a significant and strong effect on both action planning and action control, suggesting a synergistic effect on the individual factors, as well as increasing the explained variance of PA. Results confirmed the important role of received social support in the PA of CAD patients. It could be presumed that strengthening the social support from family and friends could support the regular physical activity of CAD patients.

The Role of Intra-Amygdaloid Neurotensin and Dopamine Interaction in Spatial Learning and Memory.

Neurotransmitter and neuromodulator neurotensin (NT) has been proved to facilitate spatial and passive avoidance learning after microinjected into the rat central nucleus of amygdala (CeA). These previous studies of our laboratory also revealed that neurotensin-1 receptor (NTS1) is involved in the mentioned actions of NT. Extensive literature confirms the interaction between neurotensinergic and dopaminergic systems, and our research group also suppose that the mesolimbic dopaminergic system (MLDS) is involved in the spatial learning and memory-facilitating effect of NT in the CeA. In the present work, NT and dopamine (DA) interaction has been examined in the Morris water maze and passive avoidance tests. Rats received 100 ng NT, 5 µg dopamine D2 receptor antagonist sulpiride in itself, sulpiride as a pretreatment before NT or vehicle solution into the CeA. NT microinjection significantly decreased target-finding latency in the Morris water maze test and significantly increased entrance latency in the passive avoidance test, as was expected based on our previous findings. The DA D2 receptor antagonist pretreatment was able to inhibit both effects of NT. The results confirm the facilitatory effect of NT on spatial learning and memory and let us conclude that these actions can be exerted via the DA D2 receptors.

Intraamygdaloid Oxytocin Reduces Anxiety in the Valproate-Induced Autism Rat Model.

BACKGROUND: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder affecting about 1.5% of children, and its prevalence is increasing. Anxiety is one of the most common comorbid signs of ASD. Despite the increasing prevalence, the pathophysiology of ASD is still poorly understood, and its proper treatment has not been defined yet. In order to develop new therapeutic approaches, the valproate- (VPA) induced rodent model of autism can be an appropriate tool. Oxytocin (OT), as a prosocial hormone, may ameliorate some symptoms of ASD. METHODS: In the present study, we investigated the possible anxiolytic effect of intraamygdaloid OT on VPA-treated rats using the elevated plus maze test. RESULTS: Our results show that male Wistar rats prenatally exposed to VPA spent significantly less time in the open arms of the elevated plus maze apparatus and performed significantly less head dips from the open arms. Bilateral OT microinjection into the central nucleus of the amygdala increased the time spent in the open arms and the number of head dips and reduced the anxiety to the healthy control level. An OT receptor antagonist blocked the anxiolytic effects of OT. The antagonist by itself did not influence the time rats spent in the open arms. CONCLUSIONS: Our results show that intraamygdaloid OT has anxiolytic effects in autistic rats.

Novel probiotic treatment of autism spectrum disorder associated social behavioral symptoms in two rodent models.

The prevalence of autism spectrum disorder (ASD) has rapidly increased in the past decades, and several studies report about the escalating use of antibiotics and the consequent disruption of the gastrointestinal microbiome leading to the development of neurobehavioral symptoms resembling to those of ASD. The primary purpose of this study was to investigate whether depletion of the gastrointestinal microbiome via antibiotics treatment could induce ASD-like behavioral symptoms in adulthood. To reliably evaluate that, validated valproic acid (VPA) ASD animal model was introduced. At last, we intended to demonstrate the assessed potential benefits of a probiotic mixture (PM) developed by our research team. Male Wistar rats were used to create antibiotics treated; antibiotics and PM treated; PM treated, VPA treated; VPA and PM treated; and control groups. In all investigations we focused on social behavioral disturbances. Antibiotics-induced microbiome alterations during adulthood triggered severe deficits in social behavior similar to those observed in the VPA model. Furthermore, it is highlighted that our PM proved to attenuate both the antibiotics- and the VPA-generated antisocial behavioral symptoms. The present findings underline potential capacity of our PM to improve social behavioral alterations thus, indicate its promising therapeutic power to attenuate the social-affective disturbances of ASD.

The antipsychotic drug sulpiride in the ventral pallidum paradoxically impairs learning and induces place preference.

Sulpiride, as a D2-like dopamine (DA) receptor (D2R) antagonist, is an important antipsychotic drug in the treatment of schizophrenia. Recently, we have shown that the activation of D2Rs in the ventral pallidum (VP) modulates the activity of the ventral tegmental area (VTA) DAergic neurons. According to our hypothesis, intra-VP sulpiride can influence the motivational and learning processes, pervasively modifying the behavior of examined animals. In the present study, sulpiride was microinjected into the VP of male Wistar rats in three different doses. Morris water maze (MWM) test was applied to investigate the effects of sulpiride on spatial learning, while conditioned place preference (CPP) test was used to examine the potential rewarding effect of the drug. In order to show, whether the animals can associate the rewarding effect with an area which can be recognized only on its spatial location, we introduced a modified version of the CPP paradigm, the spatial CPP test. Our results show that the intra-VP sulpiride dose-dependently impairs learning processes. However, the largest dose of sulpiride induces place preference. Results of the spatial CPP paradigm demonstrate that the animals cannot associate the rewarding effect of the drug with the conditioning area based on its spatial location. In the CPP paradigm, locomotor activity decrease could be observed in the sulpiride-treated rats, likely because of a faster habituation with the conditioning environment. In summary, we can conclude that intra-VP sulpiride has a dual effect: it diminishes the hippocampus-dependent spatial learning processes, in addition, it has a dose-dependent rewarding effect.

Effect of D1- and D2-like Dopamine Receptor Antagonists on the Rewarding and Anxiolytic Effects of Neurotensin in the Ventral Pallidum.

BACKGROUND: Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central nervous system. It was shown previously that NT in the ventral pallidum (VP) has rewarding and anxiolytic effects. NT exerts its effect in interaction with dopamine (DA) receptors in numerous brain areas; however, this has not yet been investigated in the VP. The aim of this study was to examine whether the inhibition of D1-like and D2-like DA receptors of the VP can modify the above mentioned effects of NT. METHODS: Microinjection cannulas were implanted by means of stereotaxic operations into the VP of male Wistar rats. The rewarding effect of NT was examined by means of a conditioned place preference test. Anxiety was investigated with an elevated plus maze test. To investigate the possible interaction, D1-like DA receptor antagonist SCH23390 or D2-like DA receptor antagonist sulpiride were microinjected prior to NT. All of the drugs were also injected independently to analyze their effects alone. RESULTS: In the present experiments, both the rewarding and anxiolytic effects of NT in the VP were prevented by both D1-like and D2-like DA receptor antagonists. Administered on their own, the antagonists did not influence reward and anxiety. CONCLUSION: Our present results show that the activity of the D1-like and D2-like DA receptors of the VP is a necessary requirement for both the rewarding and anxiolytic effects of NT.

The Role of Intraamygdaloid Oxytocin and D2 Dopamine Receptors in Reinforcement in the Valproate-Induced Autism Rat Model.

BACKGROUND: autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting around 1 out of 68 children and its incidence shows an increasing tendency. There is currently no effective treatment for ASD. In autism research, the valproate (VPA)-induced autism rodent model is widely accepted. Our previous results showed that intraamygdaloid oxytocin (OT) has anxiolytic effects on rats showing autistic signs under the VPA-induced autism model. METHODS: rats were stereotaxically implanted with guide cannulae bilaterally and received intraamygdaloid microinjections. In the present study, we investigated the possible role of intraamygdaloid OT and D2 dopamine (DA) receptors on reinforcement using VPA-treated rats in a conditioned place preference test. OT and/or an OT receptor antagonist or a D2 DA antagonist were microinjected into the central nucleus of the amygdala (CeA). RESULTS: valproate-treated rats receiving 10 ng OT spent significantly longer time in the treatment quadrant during the test session of the conditioned place preference test. Prior treatment with an OT receptor antagonist or with a D2 DA receptor antagonist blocked the positive reinforcing effects of OT. The OT receptor antagonist or D2 DA antagonist in themselves did not influence the time rats spent in the treatment quadrant. CONCLUSIONS: Our results show that OT has positive reinforcing effects under the VPA-induced autism rodent model and these effects are OT receptor-specific. Our data also suggest that the DAergic system plays a role in the positive reinforcing effects of OT because the D2 DA receptor antagonist can block these actions.

Reduced capacity in automatic processing of facial expression in restrictive anorexia nervosa and obesity.

There is growing evidence that disordered eating is associated with facial expression recognition and emotion processing problems. In this study, we investigated the question of whether anorexia and obesity occur on a continuum of attention bias towards negative facial expressions in comparison with healthy individuals of normal weight. Thirty-three patients with restrictive anorexia nervosa (AN-R), 30 patients with obesity (OB) and 63 healthy age and social-economic status matched controls were recruited. Our results indicated that AN-R patients were more attentive to angry faces and had difficulties in being attentive to positive expressions, whilst OB patients had problems in looking for or being attentive to negative expressions independently of self-reported depression and anxiety. Our findings did not support the idea that AN-R and OB occur on a continuum. We found that AN-R was associated with a reduced capacity in positive facial expression processing, whereas OB was associated with a reduced capacity in negative facial expressions processing. The social relevance of our findings and a possible explanation based upon neuroscience are discussed.

[Functional MRI investigation of brain activity triggered by taste stimulation]. / Ízstimulációval kiváltott agyi tevékenység funkcionális MR-vizsgálata elhízásban.

INTRODUCTION: Many factors contribute to the pathogenesis of morbid obesity, and the central nervous system - as one of those - also has an important role. Numerous studies focus on the central regulation of eating and metabolism, since associated problems like obesity, anorexia, diabetes or metabolic syndrome put an increasing burden on the health system of modern societies. Neither the pathophysiologic changes, nor the normal regulation of these systems are known adequately. Functional MR (fMRI) imaging, which has certainly gained popularity recently, aims to better understand these mechanisms. In this series we studied the brain fMRI activity changes of normal and obese persons, triggered by gustatory stimulation. METHODS: 10 obese and 10 normal weight healthy volunteers took part in the study, with comparable age and sex distribution. Gustatory stimulation was performed by 0.1 M sucrose (pleasant), 0.5 mM quinine HCl (unpleasant) and complex vanilla flavored (Nutridrink) solutions, which were administered through 0.5 mm PVC tubes, in 5-5 ml portions. For rinsing distilled water with neutral flavor was used. Imaging was performed in a 3T MRI, applying standard EPI sequences. Post processing of data was accomplished by FSL software package. RESULTS: Brain activation for gustatory stimuli was characteristically different between the two groups. There were high intensity activations in more cortical and subcortical regions of the obese volunteers compared to the normal ones. CONCLUSIONS: Our current fMRI investigations revealed different activations of numerous brain regions of normal and obese individuals, triggered by pleasant and unpleasant gustatory stimulation. Based on these results this method can help to recognize the role of the central nervous system in obesity, and may contribute to develop new therapies for weight loss.

Effects of D2 dopamine receptor activation in the ventral pallidum on sensory gating and food-motivated learning in control and schizophrenia model (Wisket) rats.

Dopamine D2 receptors (D2Rs) of the ventral pallidum (VP) play important role in motivational and learning processes, however, their potential role in triggering schizophrenic symptoms has not been investigated, yet. In the present experiments the effects of locally administered D2R agonist quinpirole were investigated on behavioral parameters related to sensorimotor gating, motor activity and food-motivated labyrinth learning. Two weeks after bilateral implantation of microcannulae into the VP, the acute (30 min) and delayed (3, 21 and 24 h) effects of quinpirole microinjection (1 µg/0.4 µL at both sides) were investigated in Wistar and schizophrenia model (Wisket substrain) rats in prepulse inhibition (PPI) and the reward-based Ambitus tests. Quinpirole administration did not modify the impaired sensorimotor gating in Wisket rats, but it led to significant deficit in Wistar animals. Regarding the locomotor activity in the Ambitus test, no effects of quinpirole were detected in either groups at the investigated time points. In contrast, quinpirole resulted in decreased exploratory and food-collecting activities in Wistar rats with 21 and 24 h delay. Though, impaired food-related motivation could be observed in Wisket rats, but quinpirole treatment did not result in further deterioration. In summary, our results showed that the VP D2R activation in Wistar rats induces symptoms similar to those observed in schizophrenia model Wisket rats. These data suggest that Wisket rats might have significant alterations in the functional activity of VP, which might be due to its enhanced dopaminergic activity.