Regional brain changes in [ 3H]SCH 23390 binding to dopamine D1 receptors after long-term haloperidol treatment: lack of correspondence with the development of vacuous chewing movements

Abstract

Localized alterations in brain D1 receptors have been suggested to play a role in the development of vacuous chewing movements (VCMs) in rodents after long-term neuroleptic treatment. In the present study [ 3H]SCH 23390 binding to D1 receptors in basal ganglia and other brain regions was examined in rats showing high or low VCM levels after 21 weeks of treatment with haloperidol decanoate (HAL). D1 binding was significantly decreased in the caudate-putamen of HAL-treated rats, compared with vehicle-treated controls (−18%, P<0.001). However, this decrease occurred equally in treated rats showing high or low levels of VCMs. No changes were observed in any other brain region examined, including various subdivisions of the substantia nigra pars reticulata. D1/D2 binding ratios were significantly decreased in HAL-treated as compared to vehicle controls in all regions examined, with the exception of the olfactory tubercle. However, no differences in D1/D2 ratios between high VCM and low VCM subgroups were detected. Correlations between frequency of VCMs and D1 binding, D2 binding or D1/D2 binding ratios across brain regions were generally modest (<0.5). These results confirm the ability of long-term haloperidol to induce selective decreases in D1 binding in specific brain areas, but fail to provide evidence for a possible role of altered D1 receptor binding in the development of oral dyskinetic syndromes after long-term neuroleptic treatment.