Dopamine-transporter heterozygous rats carrying maternal wild-type allele are more vulnerable to the development of compulsive behavior

Compulsivity is defined as an unstoppable tendency toward repetitive and habitual actions, which are reiterated despite negative consequences. Polydipsia is induced preclinically by intermittent reward, leading rodents to ingest large amounts of fluids. We focused on the role of dopamine transporter (DAT) and inheritance factors in compulsive behavior. Our sample consisted of DAT heterozygous (HET) rats with different genetic inheritance (MAT-HET, born from WT-dams × KO-fathers; MIX-HET, born from HET-dams × KO-fathers). As controls, we used both wild-type (WT) rats and their socially-isolated (WTi) siblings. We ran the schedule-induced polydipsia (SIP) protocol, to induce compulsive behavior; then the Y-maze and marble-burying tests, to verify its actual development. Only MAT-HET (who inherited the functional DAT allele from the WT mother) is vulnerable to developing compulsive behavior. MAT-HET rats drank increasingly more water during SIP; they showed significant perseverance in the Y-maze test and exhibited compulsive actions in the marble-burying test. Interestingly, compulsive behaviors of MAT-HET rats correlated with expression ex vivo of different genes in different areas. Regarding the prefrontal cortex (PFC), D2R correlated with Y-maze "perseverance" in addition to BDNF; considering the amygdala (AMY), both D3R and OXTR correlated with SIP "licks." Indeed, compulsivity may be linked to D2R and BDNF in PFC, while extreme anxiety in MAT-HET rats may be associated with D3R and OXTR in the AMY. These results confirm some similarities between MAT-HET and DAT-KO subjects, and link the epigenetic context of the DAT gene to the development of compulsive behavior

The Role of Stress and Cognitive Absorption in Predicting Social Network Addiction

: Nowadays, the use of social networks (SNs) is pervasive and ubiquitous. Among other things, SNs have become a key resource for establishing and maintaining personal relationships, as further demonstrated by the emergence of the pandemic. However, easy access to SNs may be a source of addictive behaviour, especially among the younger population. The literature highlights various psychological and physiological factors as possible predictors of vulnerability to SN addiction. This paper explores the joint effects of stress level and cognitive absorption, in the form of temporal dissociation while on SNs, on the addiction of university students to SNs. Here, 312 participants were involved in an online survey. About 14% of the sample presented a risk for SN addiction. Moreover, it was found that stress level predicted SN addiction both directly and indirectly through the effect of individual temporal dissociation, as experienced during SN usage. These results suggest a significant role of perceived stress level on addiction risk, while also pointing out additional vulnerability to SN addiction for cognitive profiles that are relatively more prone to temporal dissociation while online

Bored with boredom? Trait boredom predicts internet addiction through the mediating role of attentional bias toward social networks

Internet addiction is an emerging issue, impacting people's psychosocial functioning and well-being. However, the prevalence and the mechanisms underlying internet misuse are largely unknown. As with other behavioral addiction disorders, the increase and persistence of internet addiction may be favored by negative affect such as boredom. In this study, we examined the role of boredom susceptibility, as a personality trait, in predicting the risk of internet addiction. Furthermore, we analyzed the attentional mechanisms that may exacerbate dysfunctional internet behaviors. Specifically, we assessed the mediating role of attentional bias toward social media cues on the relation between boredom susceptibility and internet addiction. Sixty-nine young adults were administered a dot-probe task assessing internet-related attentional bias (AB) and questionnaires measuring internet addiction (IAT) and boredom susceptibility (BS-BSSS). Correlation and t-test analyses confirmed that the tendency to experience boredom and selective attention toward social network information was related to internet addiction. Furthermore, the mediation model indicated that AB fully explains the link between BS-BSSS and IAT. The study highlighted the crucial role of selective attentional processing behind internet addiction. The current results are useful for both researchers and clinicians as they suggest that intervention programs for internet addiction should include strategies to cope with dysfunctional cognitive processes

Selective alterations of endocannabinoid system genes expression in obsessive compulsive disorder

Abstract Obsessive Compulsive Disorder (OCD) is listed as one of the top 10 most disabling neuropsychiatric conditions in the world. The neurobiology of OCD has not been completely understood and efforts are needed in order to develop new treatments. Beside the classical neurotransmitter systems and signalling pathways implicated in OCD, the possible involvement of the endocannabinoid system (ECS) has emerged in pathophysiology of OCD. We report here selective downregulation of the genes coding for enzymes allowing the synthesis of the endocannabinoids. We found reduced DAGLα and NAPE-PLD in blood samples of individuals with OCD (when compared to healthy controls) as well as in the amygdala complex and prefrontal cortex of dopamine transporter (DAT) heterozygous rats, manifesting compulsive behaviours. Also mRNA levels of the genes coding for cannabinoid receptors type 1 and type 2 resulted downregulated, respectively in the rat amygdala and in human blood. Moreover, NAPE-PLD changes in gene expression resulted to be associated with an increase in DNA methylation at gene promoter, and the modulation of this gene in OCD appears to be correlated to the progression of the disease. Finally, the alterations observed in ECS genes expression appears to be correlated with the modulation in oxytocin receptor gene expression, consistently with what recently reported. Overall, we confirm here a role for ECS in OCD at both preclinical and clinical level. Many potential biomarkers are suggested among its components, in particular NAPE-PLD, that might be of help for a prompt and clear diagnosis

Endocannabinoid System Regulation in Female Rats with Recurrent Episodes of Binge Eating

Recurrent Binge Eating (BE) episodes characterize several eating disorders. Here, we attempted to reassemble a condition closer to BE disorder, and we analyzed whether recurrent episodes might evoke molecular alterations in the hypothalamus of rats. The hypothalamus is a brain region which is sensitive to stress and relevant in motivated behaviors, such as food intake. A well-characterized animal model of BE, in which a history of intermittent food restriction and stress induce binge-like palatable food consumption, was used to analyze the transcriptional regulation of the endocannabinoid system (ECS). We detected, in rats showing the BE behavior, an up-regulated gene expression of cannabinoid type-1 receptor (CB1), sn-1-specific diacylglycerol lipase, as well as fatty acid amide hydrolase (Faah) and monoacylglycerol lipase. A selective reduction in DNA methylation was also observed at the promoter of Faah, which is consistent with the changes in the gene expression. Moreover, BE behavior in rats was associated with an increase in anandamide (AEA) levels. Our findings support the relevant role of the ECS in the regulation of food intake in rats subjected to repeated BE episodes, and, in particular, on AEA signaling, acting via CB1 and FAAH modulation. Notably, the epigenetic regulation of the Faah gene might suggest this enzyme as a possible target for developing new therapeutical approaches

In Search for Biomarkers in Obsessive-Compulsive Disorder: New Evidence on Saliva as a Practical Source of DNA to Assess Epigenetic Regulation

Background: Brain-Derived Neurotrophic Factor (BDNF) is a promising candidate biomarker in both the development and aetiology of different neuropsychiatric conditions, including obsessive-compulsive disorder (OCD). Most of the studies in the field have been carried out in blood cells, including peripheral blood mononucleated cells (PBMCs), although DNA of high quality can be easily isolated from saliva. Objective: The objective of this study was to evaluate the epigenetic regulation of the BDNF gene in the saliva of a clinical sample of OCD patients in order to assess this source as an alternative to blood. Methods: We first analyzed DNA methylation levels at BDNF in the saliva of subjects suffering from OCD (n= 50) and healthy controls (n=50). Then, we compared these data with the results previously obtained for the same genomic region in blood samples from the same patients and controls (CTRL). Results: Our preliminary data showed a significant reduction of 5mC levels at BDNF gene (OCD: 1.23 ± 0.45; CTRL: 1.85 ± 0.64; p < 0.0001) and a significant correlation between DNA methylation in PBMCs and saliva (Spearman r = 0.2788). Conclusion: We support the perspective that saliva could be a possible, reliable source, and a substitute for blood, in search of epigenetic biomarkers in OCD