Decreased mu-opioid receptor binding in the globus pallidus of rats treated with chronic haloperidol.
BACKGROUND
Chronic neuroleptic treatment produces a movement disorder in rats characterized by vacuous chewing movements (VCMs). Neuroleptics also produce a variety of changes in opioid neurotransmission in several regions of the basal ganglia. Rats with the VCM syndrome show elevated mRNA for enkephalin in striatopallidal neurons, suggesting a possible role for enkephalin in the pathophysiology of VCMs.


OBJECTIVE
This study investigated the role of mu-opioid receptor density in the basal ganglia on the expression of VCMs.


METHODS
Rats were treated with haloperidol for 24 weeks and withdrawn for 9 weeks. Mu (m) receptors were labeled with [3H]-DAMGO.


RESULTS
Haloperidol treatment produced a significant reduction in mu-receptor binding in the globus pallidus (P<0.05). There was, however, no relationship between mu-opioid receptor density and VCMs in this or any other region of the basal ganglia.


CONCLUSIONS
These results replicate prior findings of a neuroleptic-induced reduction in [3H]-DAMGO binding in the globus pallidus. The lack of association between VCMs and [3H]-DAMGO binding in the globus pallidus or any other region suggests that prior reports of enkephalinergic mRNA changes in the striatum are not accompanied by compensatory changes in postsynaptic neurons.
Clinical Brain Disorders Branch, NIMH, Bethesda, MD 20814-9692, USA.
C M
CM
Bower
T M
TM
Hyde
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M
Zaka
E H
EH
Hamid
S M
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Baca
M F
MF
Egan
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D004409:Dyskinesia, Drug-Induced / Q000523:psychology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013997:Time Factors
D014150:Antipsychotic Agents; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D006220:Haloperidol