Chronic blockade of D2 but not D1 dopamine receptors facilitates behavioural responses to endogenous enkephalins, protected by kelatorphan, administered in the accumbens in rats.

It has previously been shown that kelatorphan, (R)-3-(N-hydroxycarboxamido-2-benzyl-propanoyl)-L-alanine, a mixed inhibitor of the catabolism of enkephalins, injected into the nucleus accumbens, induced a dose-dependent hyperlocomotion in rats. In this study, the consequence of chronic treatment with sulpiride, a selective D2 dopamine receptor antagonist, SCH 23390, a selective D1 dopamine receptor antagonist, or haloperidol, a nonspecific but preferential D2 receptor antagonist, on the behavioural response induced by acute administration of kelatorphan into the accumbens, has been investigated in rats. The drug SCH 23390 did not modify the behavioural response to kelatorphan, whereas sulpiride and haloperidol induced an increase which was maximal in the third week after the beginning of treatment, a period corresponding to the appearance of the antipsychotic effect of the neuroleptics. This facilitation was reversed by prior administration of the delta-selective antagonist, ICI 174864. These results suggest that the phasic activity of enkephalinergic neurones of the nucleus accumbens and the associated behavioural hyperactivity are facilitated after chronic blockade of the D2 but not the D1 subtypes of dopamine receptor.