Cholinergic regulation of endogenous morphine release from lobster nerve cord.
BACKGROUND
Invertebrate nervous systems are regulated by G-coupled protein receptors, chemical transporters, and ion channels responsive to established drugs of abuse including opiates, alcohol, psychostinulants, and nicotine. Thus, invertebrate nervous tissue preparations can be used as predictive model systems by which to evaluate underlying pharmacological mechanisms of addictive processes.


METHODS
Ex vivo pharmacological trials were used to determine the comparative effects of the nicotinic agonists and antagonists on the evoked release of labeled morphine from H. americanus nerve cord. The intrinsically low basal levels of endogenous morphine required that we utilize an ex vivo model system involving pre-labeling of intracellutlar opiate alkaloid pools with high specific activity 125I labeled morphine.


RESULTS
Both nicotine and epibatidine promoted evoked release of 125I labeled morphine that is selectively linked to activation of invertebrate nicotinic receptors based on pharmacological inhibition by alpha bungarotoxin (alpha-BuTx). Epibatidine promoted release at concentrations 2-3 orders of magnitude higher than nicotine. Co-administration of nicotine (60 nM) and the pre-junctional ganglionic nicotinic antagonist hexamethonium (1 microM) produced a marked potentiation of 125I labeled morphine release; a pharmacological effect also observed for epibatidine (35 microM) co-administered with the competitive nicotinic antagonist chlorisondaminie at 1 microM. The stimulatory effects of ethanol to promote enhanced release of endogenous morphine were not affected by co-admninistration of alpha-BuTx at 1 microM.


CONCLUSIONS
The stirmulatory effects of nicotine on cellular expression and release of endogenous morphine occurs via specific alpha-BuTx sensitive receptors, suggesting a novel mechanism underling the reinforcing and addictive properties of nicotine via endogenous morphine.
Zhu
Wei
W
Neuroscience Research Institute, State University of New York-College at Old Westbury, P.O. Box 210, Old Westbury, NY 11568, USA. zhuwei@sunynri.org
Mantione
Kirk J
KJ
Casares
Federico M
FM
Sheehan
Melinda H
MH
Kream
Richard M
RM
Stefano
George B
GB
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000187:drug effects* / Q000378:metabolism; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D009020:Morphine / Q000378:metabolism*; D008121:Nephropidae / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018738:Hexamethonium; D000431:Ethanol; D009538:Nicotine; D009020:Morphine; C082748:epibatidine