PNAS 2010-01-19

Nucleus accumbens dopamine mediates amphetamine-induced impairment of social bonding in a monogamous rodent species.

Yan Liu, Brandon J Aragona, Kimberly A Young, David M Dietz, Mohamed Kabbaj, Michelle Mazei-Robison, Eric J Nestler, Zuoxin Wang

Index: Proc. Natl. Acad. Sci. U. S. A. 107(3) , 1217-22, (2010)

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Abstract

The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating, a behavior in which central dopamine (DA) has been implicated. Here, we used male prairie voles to examine the effects of drug exposure on pair bonding and related neural circuitry. In our first experiment, amphetamine (AMPH) motivated behavior was examined using a conditioned place preference (CPP) paradigm and was shown to be mediated by activation of D1-like DA receptors. Next, we examined the effects of repeated AMPH exposure on pair bonding. Intact and saline pretreated control males displayed mating-induced partner preferences, whereas males pretreated with AMPH at the doses effective to induce CPP failed to show mating-induced partner preferences. Such AMPH treatment also enhanced D1, but not D2, DA receptor expression in the nucleus accumbens (NAcc). Furthermore, pharmacological blockade of D1-like DA receptors in the NAcc rescued mating-induced partner preferences in AMPH-treated males. Together, our data indicate that repeated AMPH exposure may narrow the behavioral repertoire of male prairie voles via a DA receptor-specific mechanism in the NAcc, resulting in the impairment of pair bond formation.