TY - JOUR
T1 - D1 and D2 dopamine receptor-mediated mechanisms and behavioral supersensitivity
AU - Marin, Concepció
AU - Parashos, Sotirios A.
AU - Kapitzoglou-Logothetis, Vasiliki
AU - Peppe, Antonella
AU - Chase, Thomas N.
PY - 1993
Y1 - 1993
N2 - The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chronic DA antagonist administration were compared. Rats received either the selective D1 DA receptor antagonist SCH23390, the selective D2 DA receptor antagonist raclopride, their combination, or haloperidol, a predominatly D2 antagonist, for 21 days. Equivalent cataleptogenic doses of all drugs and drug combinations were employed. Tolerance to the cataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23390-, raclopride-, and haloperidol-treated rats. In contrast, coadministration of both SCH23390 and raclopride had no effect on apomorphine-induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to induce tardive dyskinesia and drug tolerance than those acting selectively on one or the other of these receptor subtypes.
AB - The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chronic DA antagonist administration were compared. Rats received either the selective D1 DA receptor antagonist SCH23390, the selective D2 DA receptor antagonist raclopride, their combination, or haloperidol, a predominatly D2 antagonist, for 21 days. Equivalent cataleptogenic doses of all drugs and drug combinations were employed. Tolerance to the cataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23390-, raclopride-, and haloperidol-treated rats. In contrast, coadministration of both SCH23390 and raclopride had no effect on apomorphine-induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to induce tardive dyskinesia and drug tolerance than those acting selectively on one or the other of these receptor subtypes.
KW - Behavioral supersensitivity
KW - Catalepsy
KW - Dopamine receptor interactions
KW - Neuroleptics
KW - Tardive dyskinesia
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U2 - 10.1016/0091-3057(93)90104-2
DO - 10.1016/0091-3057(93)90104-2
M3 - Article
C2 - 8516358
AN - SCOPUS:0027335608
VL - 45
SP - 195
EP - 200
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 1
ER -