The role of exogenous testosterone in cocaine-induced behavioral sensitization and plasmalemmal or vesicular dopamine uptake in castrated rats

Abstract

The possible interaction between testosterone and cocaine on behavioral and neurochemical alterations was investigated. In castrated (CAST) rats, chronic administration of testosterone propionate (TP, 2 mg/kg, s.c.) delayed and reduced chronic cocaine-induced (24 mg/kg, i.p.) focused stereotypy sensitization measured by a force-plate actometer, while the absence of TP was associated with robust behavioral sensitization to cocaine. TP itself did not produce focused stereotypy. Postmortem assays revealed that TP administration to CAST rats partially, but significantly, restored the cocaine-induced reduction of striatal plasmalemmal dopamine (DA) uptake compared to CAST rats without TP. In contrast, TP treatment did not significantly differ from the oil treatment of CAST rats in cocaine-associated enhancement of vesicular DA uptake. Thus, testosterone may modulate cocaine-induced alteration of homeostasis between extracellular and cytosolic DA pools, which may play a role in behavioral sensitization.