Modulation by enkephalin analogues and neuroleptics of apomorphine-induced stereotypy and turning behaviour in rats

The aim of the present investigation was to examine which areas of the brain might mediate the anti-apomorphine action of some opioids, which were found previously to be active upon subcutaneous application. As the first step, the substances were injected intracerebroventricularly or into the nucleus accumbens, a mesolimbic region which is rich in dopamine, and the inhibition of stereotypy induced by apomorphine was quantified. In a separate group of animals (rats with unilateral lesion of the nigra) the antagonism of turning behaviour elicited by apomorphine was measured. Substances examined were morphine, a mu-selective opiate; d-Ala 2,Nle 5-enkephalin sulphonic acid (ES), a deltaselective opioid peptide; d-Met 2Pro 5-enkephalinamide (EA), a highly potent but non-selective opioid; and two dopamine receptor blockers, haloperidol and chlorpromazine, for comparison. Examining the antagonism of turning behaviour induced by apomorphine, the order of potency was EA > haloperidol > morphine > ES ≅ chlorpromazine if injections of the substances were intracerebroventricular and EA > morphine ⪢ haloperidol ≅ ES ▪ chlorpromazine when administered into the nucleus accumbens. The order of potency for the suppression of stereotypy induced by apomorphine was EA ⪢ haloperidol > morphine > ES > chlorpromazine upon intracerebroventricular application and EA ⪢ haloperidol > morphine > ES > chlorpromazine if injected into the nucleus accumbens. The data indicate that endogenous opioids might inhibit the activity of dopamine in brain through the nucleus accumbens.