Alkylation of striatal dopamine receptors abolishes stereotyped behavior but has no effect on dopamine stimulated adenylate cyclase activity

Abstract

The role of dopamine stimulated adenylate cyclase (AC) activity in behaviours elicited by apomorphine stimulation of striatal dopamine receptors was investigated. Rats were treated with the irreversible dopamine receptor alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) alone or after pretreatment with either a D1 or D2 receptor antagonist and subsequently challenged with apomorphine. Animals that received no antagonist pretreatment showed significantly decreased striatal concentrations of D1 and D2 receptors and an abolition of apomorphine induced sniffing behaviour despite showing no change in striatal AC activity. In the groups which received antagonist pretreatment the reduction in the sniffing response paralleled the reduction in D2 receptor concentration whereas the incidence of vacuous oral movements was inversely related. In no case were the behavioural responses associated with changes in AC activity. We conclude that these behavioural effects observed in response to dopamine stimulation by apomorphine may be mediated through another second messenger system.