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The effects of clozapine on behavioural responses to the selective ‘D 1 ‐like’ dopamine receptor agonist, A 68930, and to the selective ‘D 2 ‐like’ agonist, RU 24213
Author(s) -
Daly Siobhan A.,
Waddington John L.
Publication year - 1994
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.1476-5381.1994.tb17069.x
Subject(s) - agonist , clozapine , chemistry , dopamine receptor d2 , pharmacology , receptor , spiperone , sch 23390 , endogenous agonist , dopamine , stimulation , medicine , endocrinology , dopamine receptor d1 , psychology , biochemistry , schizophrenia (object oriented programming) , psychiatry
1 The influence of the atypical antipsychotic clozapine on D 1 dopamine receptor‐mediated function was examined in terms of its effects on behavioural responses to the new isochroman selective D 1 agonist, A 68930, and to the selective D 2 agonist, RU 24213. 2 In rat striatal membrane preparations, radioligand binding studies with [ 3 H]‐SCH 23390 and [ 3 H]‐spiperone confirmed clozapine to show weak and non‐selective affinity for both D 1 and D 2 receptors. 3 Using a rapid time‐sampling behavioural check list technique, clozapine (4.0–36.0 mg kg −1 ) exerted only modest antagonism of RU 24213 (15.0 mg kg −1 )‐induced sniffing and locomotion, and weakly released some episodes of myoclonic jerking; such antagonism with release of jerking has been shown previously to occur only during concurrent stimulation of D 2 receptors and attenuation of D 1 function. 4 Over the same dose‐range, clozapine completely blocked A68930 (0.25 mg kg −1 )‐induced intense grooming but failed to influence the vacuous chewing response; this profile was similar to that demonstrated previously for selective D 1 antagonists. 5 On the basis of complete blockade of typical D 1 agonist‐induced grooming and weak release of atypical jerking to D 2 agonism in the face of modest reduction in typical D 2 ‐stimulated behaviours, clozapine apears to exert some preferential but not selective attenuation of D 1 receptor‐mediated function. Clozapine may attenuate activity through a classical D 1 receptor at a level beyond the recognition site, for which it has little affinity, or by way of new, putative ‘Dplike’ site(s) that subserve distinct elements of dopaminergic behaviour.