Effects of SK&F 83822 [3-allyl-6-chloro-7,8-dihydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine], an agonist at
dopamine D1-like receptors which stimulate
adenylyl cyclase but not
phosphoinositide hydrolysis, were studied topographically so as to clarify differences between these receptors in the regulation of behaviour. Using cloned receptors, SK&F 83822 showed high, selective affinity for
dopamine D1 and D5 over D2, D3, D4 and several non-
dopamine receptors. SK&F 83822 induced little intense grooming, but readily induced sniffing, locomotion and rearing;
seizures were evident at higher doses, characterised by tonic convulsions, forepaw
myoclonus and
explosive hyperlocomotion. The
dopamine D1-like receptor antagonist
SCH 23390 [R(+)-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] readily antagonised these responses to SK&F 83822, particularly seizure activity. The
dopamine D2-like receptor antagonist
YM 09151-2 [cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide] did not alleviate
seizures induced by SK&F 83822; YM 09151-02 did, however, attenuate SK&F 83822-induced sniffing, locomotion and rearing, and released vacuous chewing. These findings indicate that
dopamine D1-like receptors linked to
adenylyl cyclase can be differentiated from those not linked to
adenylyl cyclase in terms of their roles in the topographical regulation of behaviour. For example, the seizure and vacuous chewing responses appear to involve
dopamine D1-like receptors that stimulate
adenylyl cyclase, while intense grooming involves those which do not.