Oro-facial dyskinesia and the sub-commissural part of the globus pallidus in the cat: role of acetylcholine and its interaction with GABA.

Abstract

The possible role of cholinergic mechanisms in the sub-commissural part of the globus pallidus (scGP) in the induction of oro-facial dyskinesia (OFD) was studied in cats. Local injections of the cholinergic agonist carbachol into the scGP elicited tongue protrusions in a dose dependent way (100-1000 ng/0.5 microliters). The effect elicited by 1000 ng carbachol was selectively antagonized by the cholinergic antagonist scopolamine (10 micrograms/0.5 microliters); this dose of scopolamine was ineffective when injected alone. The tongue protrusions resulted from both normal and abnormal movements: whereas normal movements simply consisted of protruding the flat tongue, abnormal movements implied a variety of movements, especially curling upwards the lateral side(s) or tip of the tongue inside or outside the oral cavity. The abnormal carbachol-induced tongue protrusions formed part of a syndrome marked by dyskinetic movements of the muscles of the eye, ear and cheek, and were identical to those seen previously after local injections of picrotoxin (250-500 ng). Intra-pallidal injections of the abovementioned dose of scopolamine had no effect on the tongue protrusions induced by local injections of 375 ng picrotoxin. However, local injections of 100 ng muscimol, which was previously found to attenuate significantly the effect of 375 ng picrotoxin and which was ineffective when injected alone, significantly attenuated the tongue protrusions induced by local injections of 1000 ng carbachol. These data suggest that the cholinergic effects are mediated via a GABAergic mechanism, but not vice versa. The results are discussed in view of GABAergic and anti-cholinergic therapies used in oro-facial dyskinesia.