Localized changes in GABA receptor-gated chloride channel in rat brain after long-term haloperidol: relation to vacuous chewing movements.
Several lines of evidence suggest that the GABAergic system may be involved in dyskinetic side effects of long-term neuroleptic treatment. In this study, [35S]TBPS autoradiography was used to investigate changes in the GABA receptor-gated chloride ionophore in rats showing vacuous chewing movements (VCMs) after 21 weeks of treatment with haloperidol decanoate (HAL). A significant decrease in [35S]TBPS binding was observed in the globus pallidus of HAL-treated rats, compared to vehicle-treated controls (+23%, P < 0.001). However, this was equally observed in rats showing high VCM levels (> 70 counts/5 min) and those showing low VCM levels (< 30 counts/5 min), suggesting that this pallidal change cannot account for the differential development of VCMs after long-term HAL. In contrast, a small but significant increase in [35S]TBPS binding in the ventrolateral caudate-putamen was seen in animals in the high VCM group (+16%, P < 0.03), but not in those in the low VCM group, when compared to vehicle-treated controls. No significant alterations were found in other basal ganglia regions and related structures, including the substantia nigra, subthalamic nucleus, entopeduncular nucleus, and thalamic nuclei. The results are consistent with the notion of altered striatopallidal output as a result of chronic HAL treatment. They also suggest the possibility that alterations in GABA receptor-linked Cl channels in the ventrolateral caudate-putamen may contribute to the development of dyskinetic syndromes after long-term neuroleptic treatment.
Sasaki
T
T
Neurogenetics Research Section, Clarke Institute of Psychiatry, Toronto, Canada.
Kennedy
J L
JL
Nobrega
J N
JN
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects*; D018118:Chloride Channels / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects*
D018118:Chloride Channels; D018079:Receptors, GABA; D006220:Haloperidol