Premium
Pharmacological characterization of behavioural responses to SK&F 83959 in relation to ‘D 1 ‐like’ dopamine receptors not linked to adenylyl cyclase
Author(s) -
Deveney Aaron M.,
Waddington John L.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16420.x
Subject(s) - sch 23390 , adenylyl cyclase , spiperone , medicine , endocrinology , agonist , receptor , chemistry , antagonist , raclopride , dopamine receptor , stimulation , radioligand , dopamine receptor d2 , biology
1 Behavioural responses to the new benzazepine derivative, SK&F 83959, a compound that both fails to stimulate adenylyl cyclase and inhibits the stimulation of adenylyl cyclase induced by dopamine, were characterized in detail. 2 In rat striatal membrane preparations, radioligand binding studies with [ 3 H]‐SCH 23390 and [ 3 H]‐spiperone indicated SK&F 83959 had a high affinity and > 250 fold selectivity for D 1 over D 2 receptors. 3 Using a rapid time‐sampling behavioural check list technique, SK&F 83959 (0.01‐1.25 mg kg −1 ) induced grooming in the manner of all known D 1 receptor agonists, together with some vacuous chewing, which declined at higher doses with the emergence of directed chewing and rearing as an adjunct to prominent sniffing; no stereotyped behaviour was evident. 4 Grooming to SK&F 83959 (0.05 mg kg −1 ) was blocked by the selective D 1 receptor antagonists, SCH 23390 (0.01‐1.0 mg kg −1 ) and BW 737C (0.04–5.0 mg kg −1 ) and was attenuated by the selective D 2 receptor antagonist, YM 09151‐2 (0.005‐0.5 mg kg −1 ); vacuous chewing to SK&F 83959 was not influenced by either SCH 23390 or BW 737C and was enhanced by YM 09151‐2. 5 The paradoxical induction of typical D 1 receptor agonist‐induced grooming by SK&F 83959, an agent satisfying criteria for a D 1 receptor antagonist as classically defined, together with its blockade by typical D 1 antagonists, strongly suggests mediation via a ‘D 1 ‐like’ site that appears to respond similarly to agents independent of whether they exert agonist or antagonist actions at the classical adenylyl cyclase‐coupled D 1 receptor. This direct functional evidence for a ‘D 1 ‐like’ site that is not linked to adenylyl cyclase readily complements neurochemical data suggesting the existence of a cyclase‐independent ‘D 1 ‐like’ receptor that may be coupled to phosphoinositide hydrolysis.