Reduced sensitivity to cocaine effects and changes in mesocorticolimbic dopamine receptors in adolescent sexually active female rats

Rationale: The sexual behavior of the female rat is highly motivated, and the mesocorticolimbic dopaminergic system -involved in psychostimulants effects- has been implicated in its regulation. Female rats begin to express sexual behavior during adolescence, a period during which this system is not yet mature.

Objective: To examine the impact of cocaine on sexual motivation and behavior of adolescent and adult female rats, and to determine the dopamine receptors binding in mesocorticolimbic areas of these females.

Methods: The effect of acute administration of cocaine (0.0, 10.0, and 20.0 mg/kg, intraperitoneally) on the male´s incentive value for females and on their sexual behavior in late adolescent (45-55 days old) and adult (100-120 days old) rats was assessed during late proestrus. The binding of D1-like and D2-like receptors in the striatum and medial prefrontal cortex (mPFC) of adolescent and adult rats were determined by autoradiography.

Results: Cocaine did not affect females´ preference for the male. However, 10 mg/kg of cocaine reduced the expression of sexual motivated responses and 20 mg/kg also diminished sexual receptivity exclusively in adult subjects. Moreover, cocaine-induced a more pronounced hyper-locomotion in adult than in late adolescent rats. Late adolescent females exhibited higher dopamine receptors binding in the mPFC and reduced D2-like receptors binding in the Nucleus Accumbens shell when compared to adults.

Conclusions: Late adolescent females are less sensitive than adults to the detrimental effects of cocaine on sexual behavior and locomotion. This phenomenon is accompanied by variation in dopamine receptors in mesocorticolimbic areas affected by this psychostimulant.