Cellular interactions between social experience, alcohol sensitivity, and GABAergic inhibition in a crayfish neural circuit.

We report here that prior social experience modified the behavioral responses of adult crayfish to acute alcohol exposure. Animals housed individually for one week before alcohol exposure were less sensitive to the intoxicating effects of alcohol than animals housed in groups, and these differences are based on changes in the nervous system rather than differences in alcohol uptake. To elucidate the underlying neural mechanisms, we investigated the neurophysiological responses of the lateral giant (LG) interneurons after alcohol exposure. Specifically, we measured the interactions between alcohol and different GABAA-receptor antagonists and agonists in reduced crayfish preparations devoid of brain-derived tonic GABAergic inhibition. We found that alcohol significantly increased the postsynaptic potential of the LG neurons, but contrary to our behavioral observations, the results were similar for isolated and communal animals. The GABAA-receptor antagonist picrotoxin, however, facilitated LG postsynaptic potentials more strongly in communal crayfish, which altered the neurocellular interactions with alcohol, while TPMPA, an antagonist directed against GABAA-receptors with rho subunits, did not produce any effects. Muscimol, an agonist for GABAA-receptors, blocked the stimulating effects of alcohol, but this was independent of prior social history. THIP, an agonist directed against GABAA-receptors with delta subunits, which were not previously known to exist in the LG circuit, replicated the suppressing effects of muscimol. Together, our findings provide strong evidence that alcohol interacts with the crayfish GABAergic system, and the interplay between prior social experience and acute alcohol intoxication might be linked to changes in the expression and function of specific GABAA-receptor subtypes.