A genetic reduction in the serotonin transporter differentially influences MDMA and heroin induced behaviours.

Abstract

Despite ongoing study and research to better understand drug addiction, it continues to be a heavy burden. Only a small percentage of individuals who take drugs of abuse go on to develop addiction. However, there is growing evidence to suggest that a reduction in the serotonin transporter may play an important role for those that transition to compulsive drug taking. Studies have demonstrated that reduced serotonin transporter function potentiates self-administration of psychostimulant drugs ("ecstasy," MDMA; cocaine); however, additional research revealed no differences between genotypes when the opioid heroin was self-administered. These results suggest that a reduction in the serotonin transporter may confer susceptibility to the development of addiction to some classes of drugs but not others. Importantly, the mechanism underlying facilitated psychostimulant self-administration is currently unknown. Therefore, to continue investigating the relationship between compromised serotonergic function and different classes of drugs, a series of experiments was conducted investigating locomotor activity (LMA) and conditioned taste aversion (CTA) in the serotonin transporter knockout (SERT KO) rat model. MDMA-induced hyperactivity was reduced, while MDMA-induced CTA was enhanced, in SERT KO rats. However, there were no genotype differences in heroin-induced behaviours. These results reinforce the idea that a reduction in the serotonin transporter drives differential effects between disparate classes of drugs of abuse.