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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired perceptual processing and social communication, intellectual disabilities, and repetitive behaviors. Interestingly, while not a core symptom, anxiety disorders frequently co-occur in individuals with ASD and deficits in safety learning have been described in patients with anxiety-related disorders. Because genetic factors, such as SHANK deficiency (loss-of-function mutations), have been linked to ASD, the aim of the present study was to investigate whether Shank2 deficiency interferes with associative fear and safety signal learning. To first investigate trait anxiety, male and female Shank2 -deficient mice were exposed to a light-dark box test. Mice were then submitted to a combination of contextual fear conditioning and single-cue safety conditioning. The results show that Shank2 deficiency increases trait anxiety but reduces contextual fear learning. In male but not female Shank2 -deficient mice, reduced single-cued safety learning was observed. This safety learning deficit was not caused by altered anxiety levels, increased locomotor activity, or reduced contextual fear since these changes were also observed in female Shank2 -deficient mice. Concluding, our data indicate that the observed safety learning deficits in Shank2 -deficient male mice could contribute to the emotional symptoms observed in ASD and the high comorbidity with anxiety-related disorders. • Mutations in the SHANK gene have been linked to Autism Spectrum Disorder (ASD). • Shank2 -deficient mice showed increased trait anxiety. • Shank2 -deficient mice had reduced contextual fear conditioning. • Male but not female Shank2 -deficient mice showed impaired safety learning. • This emotional deficits could contribute to emotional symptoms of ASD. [ABSTRACT FROM AUTHOR]

Highlights • Generalization of contextual fear memory is used as a mouse model of PTSD. • An incubation time of 4 weeks leads to fear memory generalization. • This process was not affected by gender or neuropeptide S receptor deficiency. • However, corticosterone plasma levels were increased after incubation time. • This increase was significantly higher in neuropeptide S receptor-deficient mice. Abstract One-trial contextual fear conditioning in laboratory mice results in a fear memory which is relatively specific to the original conditioning context shortly after conditioning but becomes more unspecific after an incubation time of one month. This process is called generalization of fear memory and is used to investigate processes which might be involved in the pathogenesis of post-traumatic stress disorder. In the present study, we investigated the effects of sex and neuropeptide S receptor (NPSR) deficiency in one-trial contextual fear conditioning. In addition to contextual fear, we also measured startle reactivity, anxiety and corticosterone plasma levels of the mice. Our data show main effects of sex and NPSR-deficiency on freezing behavior, startle magnitude, and anxiety levels. However, generalization of contextual fear memory after incubation time was not affected by sex. Notably, NPSR-deficient mice had a more specific fear memory shortly after conditioning than their wildtype littermates but after incubation time, all genotypes had a generalized fear memory. The present data further show that plasma corticosterone levels are increased after incubation time. This increase was significantly more pronounced in NPSR-deficient mice. Taken together, our study confirms the suitability of one-trial contextual fear conditioning to study the effects of incubation time on fear memory generalization but also indicates the need for control groups without incubation. We further demonstrate that the increase of plasma corticosterone levels after incubation time is exaggerated in NPSR-deficient mice. The latter finding suggests an important role of the NPS system in the regulation of corticosterone release. [ABSTRACT FROM AUTHOR]

Relief learning is the association of a stimulus with the offset of an aversive event. Later, the now conditioned relief stimulus induces appetitive-like behavioral changes. We previously demonstrated that the NMDA receptors within the nucleus accumbens (NAC) are involved in relief learning. The NAC is also important for reward learning and it has been shown that reward learning is mediated by an interaction of accumbal dopamine and NMDA glutamate receptors. Since conditioned relief has reward-like properties, we hypothesized that (a) acquisition of relief learning requires the activation of dopamine D1 receptors in the NAC, and (b) if D1 receptors are involved in this process as expected, a concurrent dopamine D1 and NMDA receptor activation may mediate this learning. The present study tested these hypotheses. Therefore, rats received intra-NAC injections of the dopamine D1 receptor antagonist SCH23390 and the NMDA antagonist AP5, either separately or together, at different time points of a relief conditioning procedure. First, we showed that SCH23390 dose-dependently blocked acquisition and the expression of conditioned relief. Next, we demonstrated that co-injections of SCH23390 and AP5 into the NAC, at doses that were ineffective when applied separately, blocked acquisition but not consolidation or expression of relief learning. Notably, neither of the injections affected the locomotor response of the animals to the aversive stimuli suggesting that their perception is not changed. This data indicates that a co-activation of dopamine D1 and NMDA receptors in the NAC is required for acquisition of relief learning. [ABSTRACT FROM AUTHOR]

Preparations of Ficus platyphylla are used in Nigeria’s folk medicine to manage a plethora of diseases including, insomnia, psychoses, depression, epilepsy, pain and inflammation. In this study, we examined the effects of the standardized methanol extract of F. platyphylla stem bark (FP) on apomorphine-induced changes in prepulse inhibition and locomotor activity in rats, as well as on the retrieval of a conditioned reaction in one-way active avoidance in mice. FP did not affect basal prepulse inhibition, but significantly reduced locomotor activity. The apomorphine-induced prepulse inhibition deficit and hyperactivity were significantly reversed by co-administration of clozapine or FP. Furthermore, FP inhibited the retrieval of a conditioned avoidance reaction. Our results revealed that FP contains psychoactive ingredients with neuroleptic-like properties, thus supporting the isolation and development of the biologically active components of this medicinal plant as antipsychotic agents. [ABSTRACT FROM AUTHOR]

Highlights: [•] The amygdala is important for acquisition and expression of conditioned fear. [•] SSTR2 is expressed in the amygdala, however, its role is poorly understood. [•] We show that amygdaloid SSTR2 is important for the expression of conditioned fear. [•] However, amygdaloid SSTR2 seems to play no role in fear acquisition. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance The plant arctic root (Rhodiola rosea, L.) is growing in northern regions of Europe, Asia and North America. Extracts of R. rosea are used in traditional medicine for various conditions related to nervous system function. According to scientific studies from the last decades, the plant might have potential for use in the treatment of memory impairments, stress and depression, but reports concerning other neuropsychiatric disorders are scarce. Aim of the study In this context, our study aimed to examine potential antipsychotic-like effects of R. rosea root extract. Materials and methods We tested the effects of R. rosea root extract on prepulse inhibition in rats and mice. Prepulse inhibition is an established operational measure of sensorimotor gating, which is impaired in schizophrenia and other psychotic disorders. Results R. rosea root extract increased prepulse inhibition in rats and mice. Interestingly, the R. rosea extract had stronger effects in those individual animals that had low baseline levels of prepulse inhibition. Therefore, we performed further experiments in which we pharmacologically induced a prepulse inhibition deficit by two different psychostimulants, either the dopamine D2 receptor agonist apomorphine or the NMDA receptor antagonist dizocilpine (MK-801). Pre-treatment with the R. rosea extract significantly restored both, apomorphine- and dizocilpine-induced prepulse inhibition deficits. Conclusions The present study demonstrates that R. rosea extract robustly reverses prepulse inhibition deficits in rodents. This suggests antipsychotic-like effects of R. rosea extract. Future studies should focus on the pharmacological mechanisms underlying these effects. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Sex difference has been reported in several behavioral endophenotypes of neuropsychiatric disorder in both rodents and humans. However, sex difference in cognitive symptoms associated with neuropsychiatric disorders has not been studied in detail. In this study, we induced cognitive impairment using the NMDA receptor antagonist, dizocilpine (MK-801), in male and female C57BL/6 J mice and performed a visual discrimination task in an automated touchscreen system. We found that discrimination performance decreased with increased doses of MK-801 in both sexes. However, female mice showed stronger deficit in discrimination performance than the male mice especially after administration of low (0.01 mg/kg) and high (0.15 mg/kg) doses of MK-801. Furthermore, we tested if administration of orexin A, orexin-1 receptor antagonist SB-334867 or orexin-2 receptor antagonist EMPA rescued MK-801 (0.15 mg/kg) induced cognitive impairment in visual discrimination. We found that nasal administration of orexin A partially rescued the cognitive impairment induced by MK-801 in females but not in males. Taken together, our data show that female C57BL/6 J mice are more sensitive compared to males to some doses of MK-801 in discrimination learning task and that orexin A partially rescues this cognitive impairment in females. [ABSTRACT FROM AUTHOR]

Relief learning refers to the association of a stimulus with the relief from an aversive event. The thus-learned relief stimulus then can induce, e.g., an attenuation of the startle response or approach behavior, indicating positive valence. Previous studies revealed that the nucleus accumbens is essential for the acquisition and retrieval of relief memory. Here, we ask whether the nucleus accumbens is also the brain site for consolidation of relief memory into a long-term form. In rats, we blocked local protein synthesis within the nucleus accumbens by local infusions of anisomycin at different time points during a relief conditioning experiment. Accumbal anisomycin injections immediately after the relief conditioning session, but not 4 h later, prevented the consolidation into long-term relief memory. The retention of already consolidated relief memory was not affected by anisomycin injections. This identifies a time window and site for relief memory consolidation. These findings should complement our understanding of the full range of effects of adverse experiences, including cases of their distortion in humans such as post-traumatic stress disorder and/or phobias. [ABSTRACT FROM AUTHOR]