Muscimol injected into the medial prefrontal cortex of the rat alters ethanol self-administration.

The role of the rodent prefrontal cortex in the regulation of ethanol self-administration has not been widely explored. Understanding the role of GABAergic transmission in this area in relation to ethanol self-administration is important, as the GABA system may be one of several targets for alcohol's actions in the brain. Rats were initiated to drink 10% ethanol from a dipper using a sucrose-substitution procedure. When baseline behavior was stable, bilateral microinjections of muscimol (a GABA(A) agonist) into the prefrontal cortex were tested at doses of 17.5, 30, 100 and 300 ng/microl. Ethanol self-administration was decreased by approximately 40% at the 30-ng dose and 30% at the 100-ng dose. No effects were observed at either the 17.5- or 300-ng dose. The effect on the pattern of self-administration was to shorten the size of the first run of drinking without affecting the rate of drinking. The hypothesis is put forward that the injections increased glutamatergic output to the nucleus accumbens (nAcc) that in turn increased accumbens output. This increased output is proposed as similar to the effects of dopaminergic (DA) manipulations within this system.