Background: Invertebrates express regulatory receptors, transporters, andchannels responsive to established drugs of abuse, many of which mediate their effects through catecholaminepathways. We hypothesized that invertebrate neural systems may serve as models by which to evaluate theinteractive pharmacological effects of these agents. Material/Methods: Ex vivo pharmacological trialsdetermined the effects of saturating levels of ethanol on morphine levels in pooled Mytilus edulis gangliavia HPLC coupled to electrochemical detection and/or HPLC/RIA analyses. Additional trials evaluated theability of ethanol, nicotine, and cocaine, to promote evoked release of [sup]125[/sup]I-labeled morphine fromneural tissues, because intrinsically low levels of morphine did not allow direct quantification of itsrelease. Results: Incubation of pooled M. edulis pedal ganglia with 200 mM ethanol (approximately 1%ethanol v/v) resulted in a two-fold increase in morphine concentration at 15 min, return to baselineat 30 min, and a 50% decrease in morphine concentration at 60 min. Separate incubations of pooled M.edulis pedal ganglia and H. americanus nerve cord with ethanol, cocaine, and nicotine resulted in a statisticallysignificant enhancement of [sup]125[/sup]I-trace labeled morphine release. Conclusions: The stimulatory effectsof ethanol, nicotine, and cocaine on cellular expression and release of endogenous morphine suggest convergentmechanisms underlying the reinforcing and addictive properties for a variety of drugs of abuse. The evolutionaryconservation of L-tyrosine as a common precursor to catecholamine and opiate/opioid signaling systemsmay define a functional triad involving endogenous morphine, dopamine, and other classes of addictivedrugs.

Keywords: Cocaine - pharmacology, Drug Evaluation, Preclinical - methods, Ethanol - pharmacology, Ganglia, Invertebrate - physiology, Morphine - metabolism, Mytilus edulis, Nephropidae - physiology, Nicotine - pharmacology, Street Drugs - pharmacology