One year treatment with haloperidol or clozapine fails to alter neostriatal D1- and D2-dopamine receptor sensitivity in the rat.
Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D1-agonist (+)-SKF 38393 or the D2-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 microM) and quinpirole (1 microM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D2-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D1- and D2-neostriatal receptors.
Ashby
C R
CR
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794.
Hitzemann
R
R
Rubinstein
J E
JE
Wang
R Y
RY
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D003984:Dibenzazepines / Q000494:pharmacology*; D004357:Drug Synergism; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D014150:Antipsychotic Agents; D001552:Benzazepines; D003984:Dibenzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005576:Colforsin; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D003024:Clozapine; D006220:Haloperidol