Reduced salivary oxytocin after an empathic induction task in Intimate Partner Violence perpetrators: Importance of socio-affective functions and its impact on prosocial behavior.

Intimate Partner Violence (IPV) has been linked to difficulties in socio-affective functions. Nevertheless, the underlying psychobiological mechanisms that might be responsible for them remain unclear. Oxytocin (OXT) stands out as an important hormone that may favor the salience of social information, due to its relevance in empathy and prosocial behavior. Thus, the study of salivary OXT (sOXT) may provide further information about potential impairments in social cognition in IPV perpetrators. This study analyzed the effects of an empathic induction task, performed through negative emotion-eliciting videos, on endogenous sOXT levels, mood state, and emotional perception in 30 IPV perpetrators compared to 32 controls. Additionally, we explored their performance on prosocial behavior after the empathic induction task, using Hare's donation procedure. Lower sOXT levels were found in IPV perpetrators after the task compared to controls, along with a general decreasing tendency in their sOXT levels. Additionally, IPV perpetrators exhibited no change in their mood state and perceived others' emotions as more positive and less intense. Moreover, the mood state response and alexithymia traits, respectively, positively and negatively predicted the sOXT levels after the empathic induction task in the entire sample. Finally, we did not observe a lower appearance of prosocial behaviors in IPV perpetrators; however, higher sOXT levels after the empathic induction task were found in subjects who donated when considering the whole sample. In sum, IPV perpetrators exhibited differences in their sOXT levels when empathizing, compared to controls, with alexithymia and the emotional response potentially explaining the sOXT levels after the task. Furthermore, prosocial behavior was more related to these sOXT levels than to IPV. As our knowledge about the emotional processing of IPV perpetrators increases, we will be better able to develop and include coadjutant treatments in current psychotherapeutic programs, in order to focus on their emotional needs, which, in turn, would reduce the future risk of recidivism.

Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates.

Alzheimer's disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic ß amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment.

Critical role of TLR4 in uncovering the increased rewarding effects of cocaine and ethanol induced by social defeat in male mice.

BACKGROUND: Substance use disorders and social stress are currently associated with changes in the immune system response by which they induce a proinflammatory state in neurons and glial cells that eventually modulates the reward system. AIMS: The aim of the present work was to assess the role of the immune TLR4 (Toll-like receptors 4) and its signaling response in the increased contextual reinforcing effects of cocaine and reinforcing effects of ethanol (EtOH) induced by social defeat (SD) stress. METHODS: Adult male C57BL/6 J wild-type (WT) mice and mice deficient in TLR4 (TLR4-KO) were assigned to experimental groups according to stress condition (exploration or SD). Three weeks after the last SD, conditioned place preference (CPP) was induced by a subthreshold cocaine dose (1 mg/kg), while another set underwent EtOH 6% operant self-administration (SA). Several inflammatory molecules were analyzed in the hippocampus and the striatum. RESULTS: SD induced higher vulnerability to the conditioned rewarding effects of cocaine only in defeated WT mice. Similarly, defeated WT mice exhibited higher 6% EtOH consumption, an effect that was not observed in the defeated TLR4-KO group. However, the motivation to obtain the drug was observed in both genotypes of defeated animals. Notably, a significant upregulation of the protein proinflammatory markers NFkBp-p65, IL-1ß, IL-17 A and COX-2 were observed only in the defeated WT mice, but not in their defeated TLR4-KO counterparts. CONCLUSIONS: These results suggest that TLR4 receptors mediate the neuroinflammatory response underlying the increase in the rewarding effects of cocaine and EtOH induced by social stress.

Text mining and expert curation to develop a database on psychiatric diseases and their genes.

Database URL: http://www.psygenet.org. PsyGeNET corpus: http://www.psygenet.org/ds/PsyGeNET/results/psygenetCorpus.tar.

Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder.