Abstract
Brain opioid systems modulating basal ganglia function may be involved in the development of neuroleptic-induced orofacial dyskinesias. This study examined changes in μ opioid receptors labeled with [3H]D-Ala2, N-MePhe4, Gly-ol5-enkephalin ([3H]DAMGO) in 79 different brain regions of rats showing vacuous chewing movements after 21 weeks of treatment with haloperidol decanoate (HAL). Dopamine D2 receptors labeled with [3H]raclopride were also examined in the adjacent sections of the same brains. For brain analyses HAL-treated rats were divided into a group showing high incidence of vacuous chewing movements (VCMs) and a group showing low incidence of VCMs. As expected, long-term HAL resulted in a pronounced elevation of D2 receptors in caudate-putamen, n. accumbens, globus pallidus and olfactory bulbs (range: 27–70% increases) compared to controls. These changes were equal in magnitude in both HAL-treated groups, irrespective of the frequency of VCMs. In HAL-treated rats [3H]DAMGO was significantly decreased in several parts of the basal ganglia, including n. accumbens (−21%, P < 0.01), patchy area of the anterior caudate-putamen (−12%, P < 0.05), ventral pallidum (−27%, P < 0.01) and globus pallidus (−21%, P < 0.02). Statistically significant decreases were also seen in the subthalamic nucleus (−12%, P < 0.05) and ventrolateral thalamus (−21%, P < 0.05), both of which are targets of basal ganglia output. However, as in the case of [3H]raclopride binding, [3H]DAMGO changes were generally seen both in the High VCM and the Low VCM groups. These results confirm that long-term haloperidol leads to a decrease in μ-opioid binding in basal ganglia and related structures, similar to what is seen after 6-OHDA denervation. The observed μ-receptor binding changes may be a contribution factor, but do not appear sufficient to account for the differential development of neuroleptic-induced vacuous chewing movements.
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Received: 2 February 1996 / Final version: 10 June 1996
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Sasaki, T., Kennedy, J. & Nobrega, J. Autoradiographic mapping of μ opioid receptor changes in rat brain after long-term haloperidol treatment: relationship to the development of vacuous chewing movements. Psychopharmacology 128, 97–104 (1996). https://doi.org/10.1007/s002130050115
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DOI: https://doi.org/10.1007/s002130050115