DOES COCAINE-INDUCED AGGRAVATION OF DEPRESSION ALTER MATE ATTRACTIVENESS IN MALES?

Abstract Social defeat stress is a recognized method to induce depressive-like behaviors in mice. Our study found that when mice subjected to social defeat stress were later administered with cocaine, their depressive state significantly worsened. Notably, the typical anti-depressive effects gained from overexpressing DFosB in the nucleus accumbens (NAc), a region known for mediating anti-depressive states, failed to counteract the exacerbating effects of cocaine. Interestingly, a pre-treatment involving electrical shocks to the brain triggered the induction of endogenous DFosB, generating an anti-depressive effect. Nevertheless, even in this mitigated state, subsequent cocaine administration reinstated the depressive behaviors. To robustly verify the intensification of the depressive state, behavioral paradigms like the elevated plus maze and forced swim test were conducted both before and after cocaine treatment. A notable deterioration in performance was observed specifically in the forced swim test post-cocaine administration. Given our understanding that male attractiveness in mice is influenced by physical appearance and perceived confidence, we postulated how this intensified depressive state might affect a male's attractiveness. Observations revealed that during the depressive state induced by social defeat, dopaminergic neurons in the ventral tegmental area (VTA) exhibit hyperactivity. Building on this, we employed a retrograde AAV DIO Gi and Gq injection into the NAc of TH-cre mice. The objective is to delineate the impact of dopaminergic neuron activity on both male attractiveness and the depressive state under the combined influence of social defeat and cocaine. In conclusion, this study illuminates the intricate relationship between cocaine, social defeat-induced depression, and male attractiveness, providing crucial insights into the underlying neurobiological mechanisms and potential therapeutic interventions.