Sex differences in dopamine binding and modafinil conditioned place preference in mice

Abstract

Background: Studies in humans and rodents have demonstrated under certain conditions some reinforcing properties of modafinil, a drug being examined clinically for its potential to treat psychostimulant abuse. However, the majority of rodent studies examining the abuse potential of modafinil have used high doses that may not be clinically relevant. In fact, recent work has indicated that doses similar to those administered to humans are not reinforcing in mice.

Methods: The current study examined sex differences in the ability of low-dose modafinil (0.75mg/kg, IP) to induce a conditioned place preference in mice, and assessed sex-dependent alterations in dopamine D1, D2 and DAT binding sites in reward-related regions in naïve and modafinil-treated mice.

Results: Low-dose modafinil failed to induce a conditioned place preference in male mice, while female mice demonstrated a significant modafinil place preference. Several dopamine binding differences were also detected in naïve and modafinil-treated mice, including sex differences in D1 and D2 availability in reward-related regions, and are discussed in relation to sex-dependent differences in the reinforcing effects of modafinil and psychostimulants in general.

Conclusions: These findings implicate sex differences in the reinforcing properties of modafinil in mice, and indicate that clinical evaluation of the sex dependence of the reinforcing properties of modafinil in humans is warranted.

Keywords: Conditioned place preference; Dopamine receptor autoradiography; Dopamine transporter autoradiography; Drug conditioning; Modafinil; Psychostimulant abuse.