Alcohol-, nicotine-, and cocaine-evoked release of morphine from invertebrate ganglia: model system for screening drugs of abuse.
BACKGROUND
Invertebrates express regulatory receptors, transporters, and channels responsive to established drugs of abuse, many of which mediate their effects through catecholamine pathways. We hypothesized that invertebrate neural systems may serve as models by which to evaluate the interactive pharmacological effects of these agents.


METHODS
Ex vivo pharmacological trials determined the effects of saturating levels of ethanol on morphine levels in pooled Mytilus edulis ganglia via HPLC coupled to electrochemical detection and/or HPLC/RIA analyses. Additional trials evaluated the ability of ethanol, nicotine, and cocaine, to promote evoked release of 125I-labeled morphine from neural tissues, because intrinsically low levels of morphine did not allow direct quantification of its release.


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 baseline at 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 statistically significant enhancement of 125I-trace labeled morphine release.


CONCLUSIONS
The stimulatory effects of ethanol, nicotine, and cocaine on cellular expression and release of endogenous morphine suggest convergent mechanisms underlying the reinforcing and addictive properties for a variety of drugs of abuse. The evolutionary conservation of L-tyrosine as a common precursor to catecholamine and opiate/opioid signaling systems may define a functional triad involving endogenous morphine, dopamine, and other classes of addictive drugs.
Zhu
Wei
W
Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, NY 11568, USA.
Mantione
Kirk J
KJ
Casares
Federico M
FM
Cadet
Patrick
P
Kim
Jae Won
JW
Bilfinger
Thomas V
TV
Kream
Richard M
RM
Khalill
Sara
S
Singh
Satwinder
S
Stefano
George B
GB
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000431:Ethanol / Q000494:pharmacology*; D017952:Ganglia, Invertebrate / Q000187:drug effects* / Q000502:physiology*; D013287:Illicit Drugs / Q000494:pharmacology; D066298:In Vitro Techniques; D009020:Morphine / Q000378:metabolism*; D049880:Mytilus edulis; D008121:Nephropidae / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*
D013287:Illicit Drugs; D000431:Ethanol; D009538:Nicotine; D009020:Morphine; D003042:Cocaine