Differential behavioural interactions between the dopamine D-1 antagonist SCH 23390 and the dopamine D-2 antagonists metoclopramide and sulpiride in nonhabituated mice.
This study investigated the effects of the selective D-1 antagonist SCH 23390, when administered alone and in combination with a typical (metoclopramide) or atypical neuroleptic (sulpiride), on species-typical behaviours in nonhabituated mice. When tested singly, all three compounds caused a progressive dose-dependent inhibition of locomotion, rearing and grooming, though their potencies varied widely. Mixtures of a threshold dose of 0.01 mg/kg SCH 23390 and metoclopramide (0.05-1.25 mg/kg) interacted synergistically to promote hypomotility and to decrease rearing, but did not affect grooming. By contrast, combinations of 0.01 mg/kg SCH 23390 and sulpiride (2-10 mg/kg) resulted in a marked potentiation of grooming, but only additive reductions in horizontal and vertical movements, consistent with sulpiride and metoclopramide occluding different populations of D-2 receptors. The results show that blockade of D-1 receptors and certain populations of D-2 receptors can interact positively to modify animal motor behaviour, and add a fresh perspective to the concept that these two types of dopamine receptor normally work interdependently to control movements of the body.
Chandler
C J
CJ
Psychology Group, School of Health and Human Sciences, Hatfield Polytechnic, Herts.
Starr
B S
BS
Starr
M S
MS
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004347:Drug Interactions; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D013469:Sulpiride; D008787:Metoclopramide