Striatal dopamine autoreceptors uninfluenced by chronic administration of antidepressants.
Dopamine (DA) receptor sensitivity to apomorphine (APO) was assessed in the rat nigrostriatal system following chronic antidepressant treatment. Imipramine (IMI), iprindole (IPR) or vehicle was administered to rats for 10 days (10 mg/kg i.p., b.i.d.). Two and a half days after the last injection 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured in rat striata following injection of APO (50 or 100 micrograms/kg s.c.) or vehicle. In contrast with rats receiving chronic vehicle injections, rats chronically treated with IMI or IPR failed to exhibit a significant APO-induced fall in striatal DOPAC levels. Antidepressant-treated animals, however, exhibited significantly lower basal DOPAC levels than vehicle-treated rats. In an effort to localize the diminished APO response, DA autoreceptor sensitivity to APO was assessed in drug- and vehicle-treated animals. Employing gamma-butyrolactone (GBL) and a dihydroxyphenylalanine (DOPA) decarboxylase inhibitor to elevate striatal DOPA, the APO-induced reversal of DOPA elevation was used as an index of DA autoreceptor sensitivity. This GBL-stimulated in vivo tyrosine hydroxylation was similarly reversed by APO (125, 250 or 500 micrograms/kg i.p.) in IMI-, IPR- and vehicle-treated animals. In view of these findings, we propose that the blunted biochemical response to APO observed in animals pretreated with antidepressants does not originate as a result of alterations in the sensitivity of DA autoreceptors located on the striatal presynaptic nerve terminal.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D000928:Antidepressive Agents; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D001058:Apomorphine; D004298:Dopamine