The effects of vasopressin and oxytocin on methamphetamine : induced place preference behaviour in rats.

Abstract

Methamphetamine is a highly addictive stimulant drug whose illicit use and resultant addiction has become an alarming global phenomenon. The mesolimbic dopaminergic system in the brain, originating in the ventral tegmental area and terminating in the nucleus accumbens, has been shown to be central to the neurobiology of addiction and the establishment of addictive behaviour. This pathway, as part of the reward system of the brain, has also been shown to be important in classical conditioning, which is a learnt response. This common pathway has supported theories suggesting addiction as a case of maladaptive associative learning. Within the modulation of learning and memory, the neurohypophyseal hormones vasopressin and oxytocin have been seen to play a vital role. Vasopressin exerts a long- term facilitatory effect on learning and memory processes. Studies have shown that the stress responsive AVP V1b receptor systems are a critical component of the neural circuitry underlying emotional consequences of drug reward. Oxytocin, on the other hand, has an effect on learning and memory opposite to that of vasopressin. Previous studies have shown that oxytocin caused a decrease in heroin self-administration, as well as attenuated the appearance of cocaine-induced hyperactivity and stereotyped behaviour. Therefore, we adopted a reinstatement conditioned place preference model to investigate whether a V1b antagonist or oxytocin treatment would cause a decrease in methamphetamine seeking behaviour. Behavioural findings indicated that methamphetamine induced a change in the place preference in the majority of our animals. This change in preference was not seen after vasopressin administration in the extinction phase. On the other hand, the change in place preference was enhanced during the reinstatement phase in the animals treated with oxytocin. Striatal dopamine levels were determined, as methamphetamine is known to increase dopamine transmission in this area. Results showed that rats that received both methamphetamine and oxytocin had significantly higher striatal dopamine than those that received oxytocin alone. Western blot analysis for hippocampal cyclic AMP response element binding protein (CREB) was also conducted as a possible indicator of glutamatergic NMDA receptor activity, a pathway that is important for learning and memory. The Western blot analysis showed no changes in hippocampal pCREB expression. Overall our data led us to conclude that methamphetamine treatment can change place preference behaviour in rats and that this change may be partially restored by vasopressin antagonism, but exaggerated by oxytocin.