부산대학교 도서관

Alcohol dependence is a chronic and relapsing disease. Recent studies in the addiction field show that the glutamatergic system is one of the neurotransmitter systems most involved in the disease. Among the different pharmacological agents acting on the glutamatergic system, memantine, a partial antagonist of the NMDA receptors used to treat the cognitive deficits in patients with Alzheimer disease, seems to be a potential candidate. Moreover, memantine induces expression of BDNF and we previously showed that BDNF within the striatum is part of a homeostatic pathway regulating alcohol consumption. The aims of this work were to study the effects of systemic injections of memantine on ethanol self-administration in rats and then to test our hypothesis stating that the memantine effect on alcohol consumption is mediated via the BDNF signalling pathway. We found that memantine decreases ethanol consumption 6 and 30 h post-injection (but not glucose self-administration) and that memantine decreases the motivation to self-administer ethanol at 6 h post-injection. We also found that inhibition of the BDNF receptor TrkB by intracerebroventricular micro-infusion of K252a 2 h after the memantine injection totally blocks the decrease induced by memantine, suggesting that the memantine effect on alcohol consumption is mediated by the BDNF signalling pathway. In a therapeutic perspective, memantine seems to be a serious candidate for the treatment of alcohol dependence.