Methamphetamine and α-pyrrolidinopentiophenone (α-PVP) Intravenous Self-Administration in Female and Male Rats.

Background: Stimulant drug users vary in their substance of choice and may, in some cases, switch up their preferred substance based on availability, cost or other factors. Poly-substance use is rarely assessed in rodent models of drug seeking and this study determined if training drug alters the apparent reinforcing properties of methamphetamine (MA) and α-pyrrolidinopentiophenone (α-PVP). Methods: Female and male Wistar rats (N=8 per group) were trained in the intravenous self-administration (IVSA) of α-PVP or MA. The impact of dose substitution (0.0125, 0.0250, 0.100, 0.300 mg/kg/infusion) for each training drug was then assessed in all groups under FR and Progressive Ratio schedules of reinforcement. Results: Male and female rats obtained similar numbers of infusions of MA (0.05 mg/kg/infusion) and of α-PVP (0.05 mg/kg/infusion) during acquisition, however more infusions of α-PVP than of MA were obtained by each sex. Mean lever discrimination ratios exceeded 80% on the drug-associated lever within 5 training sessions for α-PVP groups but were not consistently at this level for either MA group. Drug potency was similar across groups but was less effective in the MA-trained males. Conclusions: Interpretations of sex differences in the acquisition of drug IVSA require caution when dose is not varied across or within group. This study also further confirms that the apparent efficacy of a drug as a reinforcer depends at least partially on the behavioral antecedents, including the identity of the drug used for initial IVSA acquisition.