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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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Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

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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Abbreviations

AMPA:

alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate

COMT:

catechol-O-methyltransferase

DA:

dopamine

DOPAC:

3,4-dihydroxyphenylacetic acid

5-HT:

serotonin

5-HIAA:

5-hydroxyindoleacetic acid

HVA:

homovanillic acid

MAO:

monoamine oxidase

1MeTIQ:

1-methyl-1,2,3,4-tetrahydroisoquinoline

MHPG:

3-methoxy-4-hydroxyphenylglycol

3-MT:

3-methoxytyramine

NA:

noradrenaline

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Cracov, Poland

    L. Antkiewicz-Michaluk, J. Michaluk, I. Romańska & J. Vetulani

  2. Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracov, Poland

    M. Filip & E. Przegaliński

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  1. L. Antkiewicz-Michaluk
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Antkiewicz-Michaluk, L., Filip, M., Michaluk, J. et al. 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. J Neural Transm 114, 307–317 (2007). https://doi.org/10.1007/s00702-006-0546-y

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