The Effects of Cocaine on the Expression of Brain‐Derived Neurotrophic Factor in Female Rat Reward Circuits

Abstract

Cocaine is a highly addictive psychostimulant drug with a high relapse rate. Studies have shown that women have greater subjective responses to cocaine depending on the hormonal phase they are in, making them more susceptible to addiction. Literature shows that sex hormones can modulate the activities of Brain‐Derived Neurotrophic Factor (BDNF). BDNF modulates the growth and survival of neurons in areas such as the nucleus accumbens (NAc) and prefrontal cortex, specifically the pre‐limbic cortex (PL). However, it is still unknown how hormonal stages influence the expression of BDNF in the different phases of cocaine addiction development: self‐administration, extinction and reinstatement. We hypothesized that the expression of BDNF in the NAc and PL varies depending on the hormonal stage, as well as the stage in the development of cocaine addiction. To determine this, female adult rats were subjected to 12 sessions of short‐access self‐administration of cocaine, 16 sessions of extinction and a session of cue‐primed reinstatement. Tissue from the PL and NAc were extracted to compare the expression of BDNF after each phase of cocaine addiction. Preliminary data suggests that BDNF decreases in the NAc during low‐hormonal phases (Diestrus and Metestrus), while it increases during high‐hormonal phases (Estrus and Proestrus). In addition, BDNF protein levels seem to be elevated in the prelimbic cortex after cue‐primed reinstatement, but further analysis is required to confirm this observation. These findings suggest that BDNF expression depends on the phase of cocaine addiction and the estrous cycle in female rats. Support or Funding Information Funding was received from the following sources: UPR PRISE Program: #R25GM096955; Start up funds from Ponce Research Institute; Rise Program: NIH‐NIGMS #2R25GM082406; B.R.A.I.N. and M.A.G.I.C. Core: NIM‐HD MD007579.