In vivo comparisons of the effects of quinpirole and the putative presynaptic dopaminergic agonists B-HT 920 and SND 919 on striatal dopamine and acetylcholine release.
The extent to which the putative dopamine (DA) autoreceptor agonists B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5d]azepine dihydrochloride) and SND 919 (2-amino-4,5,6,7-tetrahydro-6-propylamino- benzthiazol dihydrochloride) and the potent D2 receptor agonist quinpirole have differential effects on pre- and postsynaptic DA receptors was determined by using in vivo microdialysis to monitor the effects of these compounds on extracellular concentrations of DA and acetylcholine (ACh) in the striata of freely moving rats. B-HT 920 and SND 919 reduced interstitial concentrations of DA, but not ACh, when administered s.c. at doses of 0.05 and 0.1 mg/kg. Quinpirole (0.05 and 0.2 mg/kg) decreased extracellular concentrations of both DA and ACh. Hence, relative to its effects on DA, quinpirole was more potent than the other drugs at DA receptors controlling ACh release. These results are consistent with the hypothesis that B-HT 920 and SND 919 have preferential actions on DA autoreceptors. Local application of the selective D2 receptor antagonist raclopride produced similar dose-dependent increases in DA and ACh release. It is unlikely therefore that differences in the degree to which endogenous DA inhibits transmitter release from nigrostriatal terminals and cholinergic neurons can account for the greater sensitivity of the former to the depressant actions of systemically administered B-HT 920 and SND 919. As was the case with systemic administration, local striatal application of B-HT 920 produced larger decreases in extracellular DA than ACh.(ABSTRACT TRUNCATED AT 250 WORDS)
Robertson
G S
GS
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Tham
C S
CS
Wilson
C
C
Jakubovic
A
A
Fibiger
H C
HC
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D052160:Benzothiazoles; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine; D000077487:Pramipexole; D019257:Quinpirole; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects; D012457:Salicylamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D001381:Azepines; D052160:Benzothiazoles; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D012457:Salicylamides; D013844:Thiazoles; D019257:Quinpirole; D020891:Raclopride; C024763:talipexole; D000077487:Pramipexole; D016627:Oxidopamine; D000109:Acetylcholine; D004298:Dopamine