D-amphetamine maintenance therapy reduces cocaine use in female rats

Rationale D-amphetamine maintenance therapy is a promising strategy to reduce drug use in cocaine use disorder (addiction). In both male rats and human cocaine users, d-amphetamine treatment reduces cocaine-taking and -seeking. However, this has not been examined systematically in female animals, even though cocaine addiction afflicts both sexes, and the sexes can differ in their response to cocaine. Objectives We determined how d-amphetamine maintenance therapy during cocaine self-administration influences cocaine use in female rats. Methods In experiment 1, two groups of female rats received 14 intermittent access (IntA) cocaine self-administration sessions. One group received concomitant d-amphetamine maintenance treatment (COC + A rats; 5 mg/kg/day, via minipump), the other group did not (COC rats). After discontinuing d-amphetamine treatment, we measured responding for cocaine under a progressive ratio schedule, responding under extinction, and cocaine-primed reinstatement of drug-seeking. In experiment 2, we assessed the effects of d-amphetamine maintenance on these measures in already IntA cocaine-experienced rats. Thus, rats first received 14 IntA cocaine self-administration sessions without d-amphetamine. They then received 14 more IntA sessions, now either with (COC/COC + A rats) or without (COC/COC rats) concomitant d-amphetamine treatment. Results In both experiments, d-amphetamine treatment did not significantly influence ongoing cocaine self-administration behaviour. After d-amphetamine treatment cessation, cocaine-primed reinstatement of cocaine-seeking was also unchanged. However, after d-amphetamine treatment cessation, rats responded less for cocaine both under progressive ratio and extinction conditions. Conclusions D-amphetamine treatment can both prevent and reverse increases in the motivation to take and seek cocaine in female animals.