Hj. Coppens et al., CATALEPSY, FOS PROTEIN, AND DOPAMINE-RECEPTOR OCCUPANCY AFTER LONG-TERM HALOPERIDOL TREATMENT, Pharmacology, biochemistry and behavior, 51(2-3), 1995, pp. 175-182
During 12-week haloperidol treatment of rats, the cataleptic effect of
an additional challenge dose becomes gradually weaker. We studied whe
ther such a tolerance phenomenon is related to receptor supersensitivi
ty-thus leaving more spare receptors - to a shift in affinity of the r
eceptors towards agonist binding or to an attenuation of a postsynapti
c response to dopamine (D-2-type) receptor blockade in the rat basal g
anglia. Receptor occupancy was studied with the radioactive agonist [H
-3]N-propylapomorphine (NPA) and antagonist [H-3]N-methylspiperone (MS
PIP) to label free dopamine D-2 receptors in vivo. Fos protein served
as an index of the postsynaptic response, which was histochemically qu
antified. This study does not support the concept that dopamine recept
or supersensitivity may overcome neuroleptic receptor blockade, but th
ere may be a shift towards higher agonist binding over time. The atten
uation of Fos protein expression in the basal ganglia precedes the dev
elopment of behavioral tolerance.