Amphetamine alters behavior and mesocorticolimbic dopamine receptor expression in the monogamous female prairie vole.

We have recently established the socially monogamous prairie vole (Microtus ochrogaster) as an animal model with which to investigate the involvement of mesocorticolimbic dopamine (DA) in the amphetamine (AMPH)-induced impairment of social behavior. As the majority of our work, to date, has focused on males, and sex differences are commonly reported in the behavioral and neurobiological responses to AMPH, the current study was designed to examine the behavioral and neurobiological effects of AMPH treatment in female prairie voles. We used a conditioned place preference (CPP) paradigm to determine a dose-response curve for the behavioral effects of AMPH in female prairie voles, and found that conditioning with low to intermediate (0.2 and 1.0 mg/kg), but not very low (0.1 mg/kg), doses of AMPH induced a CPP. We also found that exposure to a behaviorally relevant dose of AMPH (1.0 mg/kg) induced an increase in DA concentration in the nucleus accumbens (NAcc) and caudate putamen but not the medial prefrontal cortex or ventral tegmental area (VTA). Finally, repeated AMPH exposure (1.0 mg/kg once per day for 3 consecutive days; an injection paradigm that has been recently shown to alter DA receptor expression and impair social bonding in male prairie voles) increased D1, but not D2, receptor mRNA in the NAcc, and decreased D2 receptor mRNA and D2-like receptor binding in the VTA. Together, these data indicate that AMPH alters mesocorticolimbic DA neurotransmission in a region- and receptor-specific manner, which, in turn, could have profound consequences on social behavior in female prairie voles.