Non-opiate beta-endorphin fragments and dopamine--I. The neuroleptic-like gamma-endorphin fragments interfere with the behavioural effects elicited by small doses of apomorphine.
In rats, the beta-endorphin fragment, 6-17 (des-enkephalin-gamma-endorphin, DE gamma E), 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 gamma-endorphin fragments with respect to counteracting apomorphine-induced behavioural changes resides in the fragment 6-17. The influence of DE gamma E appeared to be specific for dopamine systems mediating apomorphine-induced hypomotility, since DE gamma E hardly affected apomorphine-induced stereotypy and amphetamine-induced behavioural changes. These data suggest that DE gamma E 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 DE gamma E 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 DE gamma E. The significance of the present findings are discussed in relation to the neuroleptic-like and antipsychotic action of gamma-type endorphins.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship; D018823:gamma-Endorphin
D014150:Antipsychotic Agents; D004723:Endorphins; D018823:gamma-Endorphin; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine