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  • Title: Autoradiographic mapping of mu opioid receptor changes in rat brain after long-term haloperidol treatment: relationship to the development of vacuous chewing movements.
    Author: Sasaki T, Kennedy JL, Nobrega JN.
    Journal: Psychopharmacology (Berl); 1996 Nov; 128(1):97-104. PubMed ID: 8944412.
    Abstract:
    Brain opioid systems modulating basal ganglia function may be involved in the development of neuroleptic-induced orofacial dyskinesias. This study examined changes in mu 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 mu-opioid binding in basal ganglia and related structures, similar to what is seen after 6-OHDA denervation. The observed mu-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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