Exploring Possible Sex Differences in the Effort-related Actions of Drugs Affecting Dopamine Transmission

Studies of the behavioral functions of the neurotransmitter dopamine (DA) have yielded a wealth of information about its role in activational and effort-related aspects of motivation. There have been numerous studies detailing the effects of drugs that alter DA transmission in rats, which have contributed greatly to the development of animal models of motivational symptoms in human psychiatric and/ or neurological disorders. However, one limitation of these studies is that the vast majority were done in male rats and mice. Clearly, future research is needed to characterize the effects of DAergic drugs in females as well as males. Because DA receptor antagonists are commonly used in research on effort-related choice behavior, the present studies investigated the effects of three drugs that are commonly used to manipulate DA transmission (the D1 receptor antagonist ecopipam, the D2 receptor antagonist haloperidol, and the VMAT-2 inhibitor tetrabenazine (TBZ), which blocks vesicular storage) in both male and female rats. All three drugs are capable of shifting effort-based choice in rats tested on the fixed ratio 5/chow feeding choice task, decreasing lever pressing and increasing chow intake. Analyses of the dose/response curves indicated that there were no significant dose x sex interactions after administration of ecopipam or haloperidol. However, there was a dose x sex interaction in response to TBZ. TBZ was effective in males at doses of 0.5mg/kg and 1.0 mg/kg, but a 2.0 mg/kg dose was needed to affect behavior in females. Investigating sex differences in neuropsychopharmacology research may lead to more effective treatments for psychiatric disorders.