Effects of baclofen on acetylcholine metabolism in the striatum of rats

Abstract

Haloperidol decreased acetylcholine (ACh) levels in rat striatum, an effect believed to reflect removal of dopamine inhibition of ACh neurons. The resulting hyperactive cholinergic neuron released ACh at a rate in excess of its synthetic replacement. Baclofen blocked the haloperidol-induced decrease in ACh levels at a dose which did not appreciably influence nigral-striatal dopamine metabolism. This suggested a direct inhibitory effect of baclofen on striatal cholinergic neurons. The ability of repeated administration of haloperidol to reduce striatal ACh levels was restored by a single low dose of baclofen. Repeated administration of haloperidol leads to depolarization blockade of nigral-striatal DA neurons which can be reversed by hyperpolarizing agents such as GABA or baclofen (Grace and Bunney, this symposium). If the inability of repeated haloperidol to decrease striatal ACh was a reflection of an analogous depolarization blockade of striatal cholinergic neurons, its abrupt reversal would be explained by the repolarizing action of baclofen.