Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms.
Two classes of amine-aldehyde adducts, the tetrahydroisoquinoline (TIQ) and beta-carboline (THBC) compounds, have been implicated in the mechanism in the brain underlying the addictive drinking of alcohol. One part of this review focuses on the large amount of evidence unequivocally demonstrating not only the corporeal synthesis of the TIQs and THBCs but their sequestration in brain tissue as well. Experimental studies published recently have revealed that exposure to alcohol enhances markedly the endogenous formation of condensation products. Apart from their multiple neuropharmacological actions, certain adducts when delivered directly into the brain of either the rat or monkey, to circumvent the brain's blood-barrier system, can evoke an intense and dose-dependent increase in the voluntary drinking of solutions of alcohol even in noxious concentrations. That the abnormal intake of alcohol is related functionally to opioid receptors in the brain is likely on the basis of several distinct lines of evidence which include: the attenuation of alcohol drinking by opioid receptor antagonists; binding of a TIQ to opiate receptors in the brain; and marked differences in enkephalin values in animals genetically predisposed to the ingestion of alcohol. Finally, it is proposed that the dopaminergic reward pathways which traverse the meso-limbic-forebrain systems of the brain more than likely constitute an integrative anatomical substrate for the adduct-opioid cascade of neuronal events which promote and sustain the aberrant drinking of alcohol.
Myers
R D
RD
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 17834.
D000428:Alcohol Drinking; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*
D002243:Carbolines; D007546:Isoquinolines