EVALUATION OF AMANTADINE AS REGULATOR OF ADDICTIVE BEHAVIOUR IN A RAT MODEL OF MORPHINE ADDICTION

ESPINOZA GARCIA ESTEBAN; VIRGOLINI MB,; SOTOMAYOR ZARATE RAMON

Congreso; IX International Meeting of the Latin American Society for Biomedical Research on Alcohol-ism (LASBRA); 2019

Naltrexone (a non-selective opioid antagonist) is an FDA-approved drug to treat alcoholic patients, because it prevents ethanol-induced dopamine (DA) release in limbic areas resultant of the opioid-mediated removal of the tonic GABAergic inhibition exerted on these neurons. Morphine, an alkaloid derived from opium poppy, is one of the most potent analgesic substances that can also induce relaxation and euphoria but also tolerance, severe withdrawal symptoms and rewarding properties with a high risk to relapse. Like alcohol, opioids rewarding effects include pathways that involve neurotransmitters as DA, glutamate and GABA. Amantadine is a NMDA antagonist that increases DA release, with a direct effect on DA receptors and inhibition of DA reuptake, modulating glutamatergic neurotransmission which is also involved in ethanol rewarding effects. However, the effects of amantadine on the morphine-induced addiction behaviour have not been fully studied. In this study, we investigated the administration of amantadine (25mg/kg, i.p.) on morphine-induced conditioned place preference (CPP) in four groups of adult Sprague-Dawley rats. The first group received morphine (3mg/kg, i.p.) and saline (1ml/kg, i.p.), while the second received morphine and amantadine, the third amantadine and saline, and the last one was injected with saline. The conditioning phase lasted three days, injecting the assigned treatment in the morning and confining rats in one chamber for 30 minutes. After six hours, saline solution was injected, and the rats confined to the other chamber for 30 minutes. The CPP test was performed on day 4, and the results were obtained by comparing the amount of time spent in the treatment-associated chamber between the pre and post conditioning phase. In comparison to the saline group, preliminary results indicated that conditioned preference for the treatment-associated chamber was increased in the morphine and morphine-amantadine groups (p=0.04 and p=0.008, respectively), but not in the amantadine group (p=0.06). There was no difference between the morphine and morphine-amantadine groups (p=0.47). Although further experiments are necessary to confirm these results, they suggest that NMDA antagonism did not affect morphine-induced conditioned place preference, providing potential neurobiological implications in the mechanisms behind the therapeutic approaches to treat alcohol use disorders and morphine addiction.