Decreased choline acetyltransferase immunoreactivity in discrete striatal subregions following chronic haloperidol in rats

Neuronal loss within the basal ganglia has been hypothesized to play a role in movement disorders (e.g., tardive dyskinesia) that often occur following chronic neuroleptic treatment. Previous studies in animal models have provided some support to this possibility, but have not assessed regionally specific changes after chronic neuroleptic administration. The present study examined whether counts of neurons containing acetylcholine, described as large aspiny type II neurons, were altered in subregions of the corpus striatum and nucleus accumbens following chronic haloperidol administration in rats. Rats were administered haloperidol decanoate (21 mg/kg, i.m.) or vehicle every third week for 24 weeks. Following 4 weeks of withdrawal from the drug, predefined regions were examined for choline acetyltransferase (ChAT) immunoreactive (ir) cells. Compared to the vehicle group, the haloperidol group showed significant reductions in ChAT-ir cell counts in the ventrolateral striatum, nucleus accumbens core, and nucleus accumbens lateral shell. No significant differences were found in the other regions examined: dorsolateral striatum, dorsomedial striatum, ventromedial striatum, nucleus accumbens medial shell, and horizontal limb of the diagonal band. These findings indicate that there may be regionally specific alterations in ChAT-ir cells following chronic haloperidol treatment, supporting previous hypotheses of striatal cholinergic cell loss resulting from chronic neuroleptic treatment. More importantly, the regions affected (ventrolateral striatum and nucleus accumbens) are critical in the regulation of oral movements, thus suggesting that alterations in cholinergic cell activity, and perhaps actual loss of cholinergic cells in these regions, may be important in the manifestation of late-onset oral dyskinesia. (C) 2001 Wiley-Liss, Inc.