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J Neural Transm (Vienna). 2007 Mar;114(3):307-17. Epub 2006 Aug 10.

An endogenous neuroprotectant substance, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), prevents the behavioral and neurochemical effects of cocaine reinstatement in drug-dependent rats.

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  • 1Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Cracov, Poland. antikiew@if-pan.krakow.pl

Abstract

Drug abuse disorder is induced by a variety of substances and results from their interaction with the brain reward system. It is characterized by a high frequency of relapse, usually associated with to craving. In this study we investigated the effects of 1-methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous compound with antidopaminergic and neuroprotective activity, on cocaine-induced reinstatement in cocaine-dependent, self-administering rats. 1-methyl-1,2,3,4-tetrahydroisoquinoline (50 mg/kg i.p.) completely inhibited the expression of reinstatement of cocaine self-administration and accompanying neurochemical changes induced by a single priming cocaine dose (10 mg/kg i.p.). The priming cocaine dose inhibited dopamine metabolism in the structures containing nerve endings (frontal cortex, nucleus accumbens, and striatum) but not in the substantia nigra and ventral tegmental area. A behaviorally active dose of 1-methyl-1,2,3,4-tetrahydroisoquinoline administered 30 min before a priming dose of cocaine significantly increased the dopamine concentration in the limbic structures, and strongly inhibited dopamine metabolism in the substantia nigra and ventral tegmental area. Cocaine also inhibited noradrenaline and serotonin metabolism, and 1-methyl-1,2,3,4-tetrahydroisoquinoline abolished the inhibition in noradrenaline metabolism, while it intensified the inhibition of serotonin metabolism. Our results strongly support the view that 1-methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous compound, has considerable potential as a drug for combating substance abuse disease through the attenuation of craving.

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