Non-opiate β-endorphin fragments and dopamine-I the neuroleptic-like γ-endorphin fragments interfere with the behavioural effects elicited by small doses of apomorphine

In rats, the β- endorphin fragment, 6-17 (des-enkephalin-γ-endorphin, DEγE), dose-dependently antagonized the reduction of the rate of locomotion and rearing induced by small doses of apomorphine. Structure-activity studies revealed that the active moiety of γ-endorphin fragments with respect to counteracting apomorphine-induced behavioural changes resides in the fragment 6-17. The influence of DEγE appeared to be specific for dopamine systems mediating apomorphine-induced hypomotility, since DEγE hardly affected apomorphine-induced stereotypy and amphetamine-induced behavioural changes. These data suggest that DEγE acts as a dopamine antagonist selectively, on those dopamine receptor systems which are stimulated by small doses of apomorphine and which may be located presynaptically. In contrast to acute treatment, administration of DEγE for 4 days resulted in an enhancement of apomorphine-induced hypomotility. Thus, the receptor systems involved in these effects of apomorphine may become supersensitive upon (sub)chronic treatment with DEγE. The significance of the present findings are discussed in relation to the neuroleptic-like and antipsychotic action of γ-type endorphins.