Amphetamine exposure alters behaviors, and neuronal and neurochemical activation in the brain of female prairie voles

Abstract

Previous studies have shown that 3-day d-amphetamine (AMPH) treatment effectively induced conditioned place preferences (CPP) and impaired pair bonding behaviors in prairie voles (Microtus ochrogaster). Using this established animal model and treatment regimen, we examined the effects of the demonstrated threshold rewarding dose of AMPH on various behaviors and their potential underlying neurochemical systems in the brain of female prairie voles. Our data show that 3-day AMPH injections (0.2 mg/kg/day) impaired social recognition and decreased depressive-like behavior in females without affecting their locomotion and anxiety-like behaviors. AMPH treatment also decreased neuronal activation indicated by the labeling of the early growth response protein 1 (Egr-1) as well as the number of neurons double-labeled for Egr-1 and corticotrophin-releasing hormone (CRH) in the dentate gyrus (DG) of the hippocampus and paraventricular nucleus of the hypothalamus (PVN) in the brain. Further, AMPH treatment decreased the number of neurons double-labeled for Egr-1 and tyrosine hydroxylase (TH) but did not affect oxytocinergic neurons in the PVN or cell proliferation and neurogenesis markers in the DG. These data not only demonstrate potential roles of the brain CRH and dopamine systems in mediating disrupted social recognition and depressive-like behaviors by AMPH in female prairie voles, but also further confirm the utility of the prairie vole model for studying interactions between psychostimulants and social behaviors.

Keywords: CRH; Egr-1; Hippocampus; PVN; Social recognition.