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.

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.

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.

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.

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.