Evaluation of potassium clavulanate on ethanol consumption and decision making in the model of ethanol dependence in mice

Abstract

Glutamate increases dopamine levels in the nucleus accumbens leading to ethanol dependence. Since glutamate transporter 1 (GLT1) is responsible for the removal of synaptic glutamate, up-regulation of GLT1 attenuates ethanol consumption. Rothstein et al. showed that beta-lactam antibiotics are potent stimulators of GLT1 expression, which is attributed to beta-lactam ring. However, use of any antibiotic for a prolonged period of time for decreasing ethanol consumption may lead to the development of antibiotic resistance. Hence, an ideal agent would be one which has both, the beta-lactam ring and no antibiotic effect. It has been previously shown that impaired decision-making may be relevant to alcoholics as it may prolong their drinking habit despite the negative consequences. It is possible that serotonergic hypofunction is associated with impaired decision-making and serotonergic compounds might improve it. Potassium clavulanate has been hypothesized to decrease glutamate levels and increases serotonin levels in the central nervous system (CNS). Hence, the objective of this study was to evaluate effects of potassium clavulanate on ethanol consumption and decision making in the model of alcohol dependence, alone and in combination with naltrexone.

Keywords: Research Letter