Adolescent chemogenetic activation of dopaminergic neurons leads to reversible decreases in amphetamine-induced stereotypic behavior.

Chronic perturbations of neuronal activity can evoke homeostatic and new setpoints for neurotransmission. Using chemogenetics to probe the relationship between neuronal cell types and behavior, we recently found reversible decreases in dopamine (DA) transmission, basal behavior, and amphetamine (AMPH) response following repeated stimulation of DA neurons in adult mice. It is unclear, however, whether altering DA neuronal activity via chemogenetics early in development leads to behavioral phenotypes that are reversible, as alterations of neuronal activity during developmentally sensitive periods might be expected to induce persistent effects on behavior. To examine the impact of developmental perturbation of DA neuron activity on basal and AMPH behavior, we expressed excitatory hM3D(Gq) in postnatal DA neurons in TH-Cre and WT mice. Basal and CNO- or AMPH-induced locomotion and stereotypy was evaluated in a longitudinal design, with clozapine N-oxide (CNO, 1.0 mg/kg) administered across adolescence (postnatal days 15-47). Repeated CNO administration did not impact basal behavior and only minimally reduced AMPH-induced hyperlocomotor response in adolescent TH-CrehM3Dq mice relative to WThM3Dq littermate controls. Following repeated CNO administration, however, AMPH-induced stereotypic behavior robustly decreased in adolescent TH-CrehM3Dq mice relative to controls. A two-month CNO washout period rescued the diminished AMPH-induced stereotypic behavior. Our findings indicate that the homeostatic compensations that take place in response to chronic hM3D(Gq) stimulation during adolescence are temporary and are dependent on ongoing chemogenetic stimulation.

Distress Signals: Age Differences in Psychological Distress before and during the COVID-19 Pandemic.

Psychological distress reached historically high levels in 2020, but why, and why were there pronounced age differences? We address these questions using a relatively novel, multipronged approach, part narrative review and part new data analyses. We first updated previous analyses of national surveys that showed distress was increasing in the US and Australia through 2017 and then re-analyzed data from the UK, comparing periods with and without lockdowns. We also analyzed the effects of age and personality on distress in the US during the pandemic. Results showed distress levels and age differences in distress were still increasing through 2019 in the US, UK, and Australia. The effects of lockdowns in 2020 revealed the roles of social deprivation and fear of infection. Finally, age-related differences in emotional stability accounted for the observed age differences in distress. These findings reveal the limitations of analyses comparing pre-pandemic and pandemic periods without accounting for ongoing trends. They also suggest that differences in personality traits such as emotional stability modulate responses to stressors. This could explain age and individual differences in both increases and decreases in distress in response to changes in the level of stressors such as those occurring prior to and during the COVID-19 pandemic.