Repeated exposure to ethanol alters memory acquisition and neurotransmission parameters in zebrafish brain

Alcohol is widely consumed worldwide and its abuse can cause cognitive dysfunction, affecting memory and learning due to several neurophysiological changes. An imbalance in several neurotransmitters, including the cholinergic and glutamatergic systems, have been implicated in these effects. Zebrafish are sensitive to alcohol, respond to reward stimuli, and tolerate and exhibit withdrawal behaviors. Therefore, we investigated the effects of repetitive exposure to ethanol (REE) and the NMDA receptor antagonist dizocilpine (MK-801) on memory acquisition and glutamatergic and cholinergic neurotransmission. Memory was assessed using the inhibitory avoidance and object recognition tasks. Brain glutamate levels and the activity of Na⁺-dependent transporters were evaluated as indexes of glutamatergic activity, while acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), enzyme activity were evaluated as indexes of cholinergic activity. Behavioral assessments showed that REE impaired aversive and spatial memory, an effect that MK-801 mimicked. Glutamate levels, but not transporter activity, were significantly lower in the REE group; similarly, REE increased the activity of AChE, but not ChAT, activity. These findings suggest that intermittent exposure to ethanol leads to impairments in zebrafish memory consolidation, and that these effects could be associated with alterations in parameters related to neurotransmission systems mediated by glutamate and acetylcholine. These results provide a better understanding of the neurophysiological and behavioral changes caused by repetitive alcohol use.