An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system

Drug abuse is a foremost public health problem. Cocaine is a widely abused drug worldwide that produces various reward-related behaviors. The mechanisms that underlie cocaine-induced disorders are unresolved, and effective treatments are lacking. Here, we found that an autophagy-related protein Becn2 is a previously unidentified regulator of cocaine reward behaviors. Becn2 deletion protects mice from cocaine-stimulated locomotion and reward behaviors, as well as cocaine-induced dopamine accumulation and signaling, by increasing presynaptic dopamine receptor 2 (D2R) autoreceptors in dopamine neurons. Becn2 regulates D2R endolysosomal trafficking, degradation, and cocaine-induced behaviors via interacting with a D2R-bound adaptor GASP1. Inactivating Becn2 by upstream autophagy inhibitors stabilizes striatal presynaptic D2R, reduces dopamine release and signaling, and prevents cocaine reward in normal mice. Thus, the autophagy protein Becn2 is essential for cocaine psychomotor stimulation and reward through regulating dopamine neurotransmission, and targeting Becn2 by autophagy inhibitors is a potential strategy to prevent cocaine-induced behaviors.

Continuity of neuro-psychomotor stimulation of children with congenital Zika syndrome

ABSTRACT Objective: Understand the continuity of stimulation of neuro-psychomotor development in children with congenital Zika syndrome. Method: Descriptive-exploratory study with theoretical support in symbolic interactionism. Between August and November 2019, 12 health professionals were interviewed in depth; and to the focus group, seven caregivers of children with the syndrome. The analysis was thematic inductive. Results: The continuation of neuro-psychomotor stimulation of children with Zika syndrome goes through: organizational difficulties (lack of doctors, professional unpreparedness, dissatisfaction and search for other services); socioenvironmental aspects (low maternal education, low socioeconomic level, difficulty in moving and lack of support); and conditions inherent to children (hospitalizations for respiratory crises, seizures, hypoactivity and social stigma). Final considerations: A strengthened support network with qualified human resources is necessary in order to provide comprehensive care and avoid the discontinuity of neuro-psychomotor stimulation of children with congenital Zika syndrome.

Comparative Study about Impact of Inadequate Psychomotor Stimulation on Neuro-Development in Pre-School Children in Rural India

Introduction: In a rural, underprivileged community, multiple factors including poverty, non-stimulating home environment and lack of parental awareness about early childhood development and early intervention lead to inadequate ‘nurturing care’ for young children, who with genetic predisposition for typical brain development may not reach their developmental potential. The present study attempts to compare and study the developmental differences between children who had adequate stimulation and those who did not during preschool period. Methods: Developmental assessment of 51 healthy children, aged 3.5 - 4.5 years with poor psychomotor stimulation (study group) and an age-matched group of 27 children attending pre-school (control group) from the same community was conducted and compared. Developmental screening was done using the DDST II screening tool. Results: The incidence of developmental delay in the study group was significantly higher; deficits were most marked in personal-social and language domain. Concept of colours, counting objects and drawing were conspicuously absent in most children. Conclusion: Improving home environment, provision of learning opportunity with available resources, and generation of awareness among parents regarding early child development and early intervention are simple, low-cost measures to improve the developmental trajectory in these children.

Oral prescription opioid-seeking behavior in male and female mice

A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug-seeking. However, intravenous models may not model oral users, and the preference to self-administer orally appears to be partially influenced by the user’s sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally self-administered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated robust cue-induced reinstatement. In separate mice we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior in the absence of postprandial or prior water self-administration training. During self-administration, we found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal steroid studies were performed in which we found divergent responses where ovariectomy enhanced and orchiectomy suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that 1) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, 2) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and 3) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.