AUTORADIOGRAPHIC MAPPING OF MU-OPIOID RECEPTOR CHANGES IN RAT-BRAIN AFTER LONG-TERM HALOPERIDOL TREATMENT - RELATIONSHIP TO THE DEVELOPMENTOF VACUOUS CHEWING MOVEMENTS

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 [H-3]D-Ala (2), N-MePhe(4), Gly-ol(5)-enkephalin ([H-3]- DAMGO) in 79 different b rain regions of rats showing Vacuous chewing movements after 21 weeks of treatment with haloperidol decanoate (HAL). Dopamine D-2 receptors labeled with [H-3]raclopride were also examined in the adjacent sectio ns of the same brains. For brain analyses HAL-treated rats were divide d into a group showing high incidence of vacuous chewing movements (VC Ms) and a group showing low incidence of VCMs. As expected, long-term HAL resulted in a pronounced elevation of D-2 receptors in caudate-put amen, n. accumbens, globus pallidus and olfactory bulbs (range: 27-70% increases) compared to controls. These changes were equal in magnitud e in both HAL-treated groups, irrespective of the frequency of VCMs. I n HAL-treated rats [H-3]DAMGO was significantly decreased in several p arts of the basal ganglia, including n. accumbens (-21%, P < 0.01), pa tchy area of the anterior caudate-putamen (-12%, P < 0.05), ventral pa llidum (-27%, P < 0.01) and globus pallidus (-21%, P < 0.02). Statisti cally 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 [H-3]raclopride binding, [H-3]DAMGO changes were generally seen both i n 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 ga nglia and related structures, similar to what is seen after 6-OHDA den ervation. The observed mu-receptor binding changes may be a contributi on factor, but do not appear sufficient to account for the differentia l development of neuroleptic-induced vacuous chewing movements.