Netrin-1 receptor deficiency protects against psychostimulant-induced behaviours in mice

Abstract

Psychostimulant drugs, such as cocaine and amphetamine, increase extracellular dopamine in certain brain regions, including those that make up the mesolimbic dopamine system. Dysfunction of this system is implicated in drug addiction. The development of the mesolimbic dopamine system involves netrins, a group of secreted proteins that guide growing axons to their targets. Mice that develop with reduced expression of deleted in colorectal cancer, a netrin-1 receptor, exhibit abnormal dopamine release in response to psychostimulant drugs. Furthermore, these mice show reduced amphetamine-induced locomotor activation when compared to wild-type mice. In this study, our objective is to further examine the drug-induced behaviours of DCC deficient mice. We compared adult DCC deficient and wild-type mice using two behavioural tests. First, we examined the locomotor response of these mice to cocaine. Second, using conditioned place preference, we assessed the rewarding effects of amphetamine. DCC deficient mice showed reduced cocaine-induced locomotor activation and diminished amphetamine-induced reward when compared to wild-type mice. Taken together, this study suggests that DCC deficiency can protect against certain psychostimulant-induced behaviours.