KETAMINE ATTENUATES CONTEXT-INDUCED REINSTATEMENT OF ETHANOL SEEKING AND NUCLEUS ACCUMBENS ACTIVATION IN MICE

Alcohol use disorder (AUD) is a significant public health concern, with high relapse rates often triggered by environmental cues previously associated with alcohol consumption. Strategies that interfere with alcohol-associated memories may reduce reinstatement of drug-seeking behavior. Ketamine, a NMDA receptor antagonist, modulates synaptic plasticity, and its use has been investigated for several psychiatric disorders. This study aimed to evaluate the effects of ketamine on context-induced reinstatement of ethanol seeking and neuronal activation in the nucleus accumbens in mice. Adult male C57BL/6J mice (n = 32) were trained in an operant ethanol self-administration protocol and subsequently re-exposed to the context without ethanol. Forty minutes before re-exposure, animals received saline or ketamine at the doses of 1, 10, or 30 mg/kg. Reinstatement of ethanol seeking was assessed by double labeling immunofluorescence for NeuN and c-Fos in the nucleus accumbens core and shell. Mice developed robust ethanol-seeking behavior, evidenced by higher responding in the active nose-poke hole. During reinstatement testing, ketamine significantly reduced active responses at doses of 1 and 10 mg/kg compared to saline-treated animals. c-Fos expression was decreased in the nucleus accumbens core at doses of 1 and 10 mg/kg, while reduced activation was observed in the shell region at all doses tested. These findings indicate that ketamine attenuates context-induced reinstatement of ethanol seeking, possibly by the decrease of neuronal activity in nucleus accumbens.