Social isolation during adolescence induced long term effects on cocaine-induced sensitization: role of WNT/B-catenin pathway

FUNES, A.; CUESTA S.; ROSSO, S.B.; PACCHIONI, A

Buenos Aires

Congreso; 2nd FALAN Congress, Federation of Latin American and Caribbean Neuroscience Societies.; 2016

Cocaine addiction is a chronic relapsing disorder mainly characterized by loss of control over drug seeking and taking. The transition between occasional use and addiction involves long-term neuroadaptations within the brain reward circuit and could start with the initial use in vulnerable individuals or those at vulnerable stages of development. Results from our laboratory indicate that in rats, five days of social isolation during adolescence (PND30-35) increases cocaine reinforcing properties in adulthood. Moreover, we recently described a novel role for Wnt/b-catenin pathway in cocaine-induced sensitization. In the present study our main goal is to evaluate if stress modifies Wnt/b-catenin pathway´s activity in order to increase cocaine-induced behavioral effects. We measure b-catenin and P-GSK3-b levels as a readout of the pathway activity. Our results show that while social isolation during adolescence increases cocaine-induced sensitization in adulthood with an increased activity of Wnt/b-catenin pathway in Nucleus Accumbens, it decreases in Prefrontal Cortex (PFC) at different times after isolation. Also, a systemic treatment with a DA antagonist reverse the impact of isolation on b-catenin levels in PFC. Therefore, our findings indicate that social isolation may increase cocaine vulnerability through changes of Wnt/b-catenin pathway activity that also involves DA neurotransmission.