Nandrolone alters the behavioral response to cocaine as well as striatal and cortical dopamine receptors of prepubertal male rats

Abstract

Nandrolone is the anabolic androgenic steroid (AAS) most used by athletes and adolescents. The use of supraphysiologic doses has been associated with dysfunction in brain areas that regulate anxiety, motivation, and reward. This study investigated if exposure to nandrolone before puberty altered anxiety- and addictive-like behaviors. Changes in dopamine type 2 receptors (D2DR) in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were also examined. Male rats received 10 daily injections of nandrolone decanoate (20 mg/kg) starting on day 28. Afterwards, they were tested in the elevated plus maze (EPM) and open field (OF). Their locomotor response (sensitization) and preference (conditioned place preference (CPP)) to cocaine (15 mg/kg) was also assessed. Nandrolone reduced anxiety and ambulation. Nandrolone-treated males also displayed sensitization to cocaine at an earlier age (day 44) than oil-treated males (day 52) and showed a 27% reduction in CPP to cocaine. Expression of D2DR in the NAc, and in the PFC of males tested for CPP was increased by nandrolone, whereas treatment with cocaine reduced accumbal D2DR. We hypothesize that nandrolone accelerates the development of the neural circuitry that regulates behavioral sensitization and reduces the rewarding property of cocaine, as manifested in the reduction of CPP. It is possible that the observed increase in accumbal D2DR may partially mediate the reduced anxiety and ambulation as well accelerate the maturation of the neural circuitry responsible for the sensitized response to cocaine.