γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

Abstract

SummaryLow doses (10 ng) of the dopamine agonist apomorphine induced hypolocomotion when injected into the nucleus accumbens of rats. This behavioral response was antagonized by local treatment with either the opioid peptide 7-endorphin (yE) or the non-opioid peptide N aacetyl-y-endorphin (AcyE) in a dose of 100 pg. High doses of apomorphine (10 ug) or amphetamine (2 ug) injected into the nucleus accumbens resulted in hyperlocomotion. This response was blocked by pretreatment with yE but not with AcyE. This effect of yE could be prevented by local treatment with naloxone. Neither peptides interfered with the apomorphine-induced stereotyped sniffing when the substances were injected into the nucleus caudatus. It is concluded that yE and AcyE differentially interact with distinct dopaminergic systems in the nucleus accumbens of the rat brain via an opioid and a non-opioid mechanism, suggesting that the peptide fragments originating from pro-opiomelanocortin may be specifically implicated in the control of dopaminergic activity in this brain area.The opioid peptide y-endorphin (yE) produces behavioral effects in rats which resemble those of neuroleptics in certain aspects (I-3). This neurolepticlike action can also be elicited by fragments of yE i.c. des-Tyr1-y-endorphin (DTyE) and desenkephalin-y-endorphin (DEyE), that are devoid of opiate activity (1,4-6). Thus, the opiate and neuroleptic-like action of yE may be mediated by distinct brain mechanisms. Research in this respect is especially focussed on brain dopamine (6-9), since neuroleptic drugs are potent blockers of dopaminergic activity (10), and opioid peptides have been implicated in the control of certain dopaminergic systems in the brain (11). Previously, we have reported that following subcutaneous administration DTyE and DEyE antagonized the hypolocomotion induced by low doses of the dopamine agonist apomorphine, while these peptides did not interfere with the hyperlocomotion and stereotyped behavior elicited by high doses of apomorphine (6,12). Subsequently, it was found that low doses of apomorphine injected directly into the nucleus accumbens resulted in hypolocomotion (13). This behavioral resonse was antagonized by pretreatment with DTyE and DEyE (7). High doses of apomorphine injected into the nucleus accumbens produced hyperlocomotion. This response was not affected by pretreatment with DEyE (14). From these studies it was concluded that ytype endorphins interfere with certain, but not all, dopaminergic systems in the nucleus accumbens.Recently, N -acetyl-y-endorphzn (AcyE) has been isolated from pituitary

The Effects of Aging on Molecular Forms of Beta- and Gamma-Endorphins in Rat Hypothalamus

“…Acetylation also alters the function of y-endorphin. When injected into the nucleus accumbens, y-endorphin and a-Nacetyi-y-endorphin interact differentially with two distinct dopamine-related behaviors [36]. Specific age-dependent alterations in post-translational processing such as induc tion of increased acetyltransferasc and carboxypcptidasc activity in all or in selected subpopulations of endorphinergic neurons would be consistent with the present data and could have pronounced effects on the biological activity of these peptides.…”

Pharmacological analysis of male rat sexual behavior

“…(2) The inhibitory effects of low doses of apomorphine injected into the LV were mediated by reductions in DA neurotransmission in the MPOA, presumably mediated by autoreceptors on DA terminals there (see [136]). (3) The dose range of apomorphme injected into the MPOA that affects sexual behavior is at least an order of magnitude lower than that previously shown to affect locomotor behavior, when injected either into the nucleus accumbens [124,127,221] or the caudate-putamen [219]. Furthermore, since the drug was microinjected dlrectly into brain tissue, accessability to systemic circulation was not a factor determining sensitivity to the drug.…”