Effect of haloperidol and (-)-sulpiride on dopamine agonist-induced hypoactivity.
High doses of dopamine D2 receptor agonists produce hyperactivity in rodents whereas low doses suppress activity. In this study, low doses of a range of dopamine agonists were examined for their effects on locomotor activity in rats. All agonists caused a dose-related hypolocomotor effect with a rank order of potency of quinelorane > (-)-quinpirole > 7-OHDPAT > PBTO. (-)-Sulpiride (1.6-160 mumol/kg), a neuroleptic with atypical properties caused a dose-related reversal of the hypolocomotor effect produced by all four agonists whereas the typical neuroleptic haloperidol (0.005-0.16 mumol/kg) did not reverse hypolocomotion. Neither sulpiride (5-16 mumol/kg) nor haloperidol (0.005-0.16 mumol/kg) affected locomotor activity per se, although haloperidol (1.6-5 mumol/kg) did reduce locomotor activity. The different behavioural profiles shown by (-)-sulpiride and haloperidol in these tests may reflect some of the clinical characteristics of these neuroleptics. The question of whether these effects can be ascribed to differential actions at dopamine receptor subtypes will only be answered when more selective dopamine receptor antagonists are developed.
Storey
V J
VJ
SmithKline Beecham Pharmaceuticals, Harlow, Essex, U.K.
Middlemiss
D N
DN
Reavill
C
C
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013469:Sulpiride / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001578:Benzopyrans; D018491:Dopamine Agonists; D004873:Ergolines; D010078:Oxazines; D011804:Quinolines; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D019257:Quinpirole; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; C047726:quinelorane