beta-Endorphin alters dopamine uptake by the dopamine neurons of the hypothalamus and striatum.
Opioid peptides have well-documented modulatory effects on the synaptic transmission of several neurotransmitters. In both hypothalamus and striatum there is dense innervation by the beta-endorphin and/or enkephalin neuronal systems, and physiologically relevant neuroregulatory interactions of these neurons occur with other important neurotransmitter neuronal systems, such as the dopaminergic tuberoinfundibular and nigroneostriatal systems. Previous reports have examined the effects of opioid peptides on release, synthesis and degradation of dopamine in these brain regions. In this report, we describe the effects of the intracerebral administration of beta-endorphin to increase dopamine (re)uptake by dopaminergic nerve terminals of the hypothalamus and striatum. The specific, high affinity uptake of [3H]dopamine by dopaminergic nerve terminals was studied in a synaptosomal preparation by pharmacological exclusion, using desmethylimipramine, of dopamine uptake into other monoaminergic nerve terminals. The augmentation of in vitro dopamine uptake in both hypothalamus and striatum following intracisternal administration of beta-endorphin is specifically mediated by opiate receptors, since it could be prevented by pretreatment with an opiate receptor antagonist, naltrexone. In hypothalamus, the increased dopamine uptake represents a primary effect of beta-endorphin on hypothalamic dopamine neurons and is not secondary to the opioid peptide-induced stimulation of prolactin secretion, since identical effects of beta-endorphin administration are seen in hypophysectomized and intact animals. The effect of beta-endorphin to increase hypothalamic dopamine uptake was not reflected by a change in the affinity constant for dopamine, but involved an increase in maximal initial velocity of uptake. Naltrexone blocked the effect of beta-endorphin to increase the Vmax for [3H]dopamine uptake by hypothalamic dopamine neurons in both intact and hypophysectomized rats. In vitro exposure of hypothalamic and striatal dopaminergic nerve terminals to a wide range of concentrations of beta-endorphin failed to reproduce the in vivo results; some concentrations of beta-endorphin produced small decreases in [3H]dopamine uptake which were not reversed by naloxone. The data of this study provide evidence for a further mechanism by which beta-endorphin may alter dopaminergic neurotransmission, namely by increasing dopamine reuptake into dopaminergic nerve endings.
D000042:Absorption; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004723:Endorphins / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000378:metabolism; D001615:beta-Endorphin
D004723:Endorphins; D009271:Naltrexone; D001615:beta-Endorphin; D004298:Dopamine