Amphetamine impairs pair bonding in a monogamous rodent: The involvement of mesolimbic dopamine and oxytocin.

摘要

In this Dissertation, the effects of amphetamine (AMPH) exposure on pair bond formation in the socially monogamous prairie vole (Microtus ochrogaster ) are characterized and the neural mechanisms that underlie these effects are investigated. As reviewed in Chapter 1, drug use and abuse have profound consequences on social behaviors, including pair bonding, in humans. Researchers have begun to use animal models to systematically examine the effects of drugs of abuse on a variety of social behaviors and have identified potential neural circuits that may be involved in these effects. However, the effects of drugs of abuse on pair bonding behavior have remained unstudied---perhaps due to the lack of an appropriate animal model. Therefore, in this Chapter, we also introduce the prairie vole as a candidate animal model for use in such studies and review the growing literature that has begun to elucidate the neurobiology of pair bonding. In Chapter 2, we establish the prairie vole as an animal model with which to study of the effects of drugs of abuse on pair bonding. We first investigate amphetamine (AMPH) reward in this species and then demonstrate that repeated exposure to AMPH impairs pair bond formation. In Chapter 3, we examine the neural mechanisms that underlie AMPH reward and the AMPH-induced impairment of pair bonding in male prairie voles. We demonstrate that the neurotransmitter dopamine (DA) acts in a receptor-specific manner in a mesolimbic brain region called the nucleus accumbens (NAcc) to mediate these behaviors. In Chapter 4, we examine the involvement of mesolimbic DA and the neuropeptide oxytocin (OT) in the effects of AMPH on pair bonding in the female prairie vole. We demonstrate that AMPH exposure alters OT and DA neurotransmission in mesolimbic brain regions and that these effects likely underlie the AMPH-induced impairment of pair bonding. Additionally, we demonstrate that site-specific treatment with OT into the prelimbic cortex restores partner preferences in AMPH-treated voles, and that this effect may be mediated through an interaction with NAcc DA. Finally, in Chapter 5, we discuss these findings and their implications in a general context and suggest future directions for related research.