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1-Methyl-1,2,3,4-Tetrahydroisoquinoline and Addiction: Experimental Studies

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Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 1))

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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 craving. In this Chapter it is demonstrated that 1-methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous compound with antidopaminergic and neuroprotective activity prevented the development of morphine dependence and morphine-induced abstinent syndrome as well as cocaine-induced reinstatement in cocaine-dependent, self-administering rats. The changes in catecholamine metabolism persist for a considerable period after cessation of cocaine self-administration suggesting a long-lasting functional impairment of dopamine and noradrenaline systems. In contrast, the changes in the serotonergic system are transient showing the lack of involvement of serotonin in long-term consequences of exposure to cocaine. The depression of dopaminergic activity in the limbic structures may be responsible for craving. The fact that 1MeTIQ elevates the concentration of dopamine preferentially in the limbic structures (nucleus accumbens) in cocaine-dependent rats may be responsible for its inhibition of ­reinstatement. The results strongly support the view that 1-methyl-1,2,3,4-­tetrahydroisoquinoline has considerable potential as a drug for combating substance abuse disease through the attenuation of craving, and suggested a possibility of clinical application of 1MeTIQ at least in morphine and cocaine addiction.

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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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Acknowledgments

Thanks are due to Dr. Jan Boksa (Department of Medicinal Chemistry, Institute of Pharmacology Polish Academy of Sciences) for synthesis of 1MeTIQ. The author thanks Polish Committee of Scientific Research (project N N401 004836) and the statutory funds of the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland for financial support.

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  1. Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, Smetna Street 12, Kraków, 31-343, Poland

    Lucyna Antkiewicz-Michaluk & Jerzy Michaluk

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  1. Lucyna Antkiewicz-Michaluk
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  2. Jerzy Michaluk
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Correspondence to Lucyna Antkiewicz-Michaluk .

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  1. Smetna 12, Krakow, 31-343, Poland

    Lucyna Antkiewicz-Michaluk

  2. , Departments of Psychiatry, Charité-University Medicine, Berlin, 10117, Germany

    Hans Rommelspacher

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Antkiewicz-Michaluk, L., Michaluk, J. (2012). 1-Methyl-1,2,3,4-Tetrahydroisoquinoline and Addiction: Experimental Studies. In: Antkiewicz-Michaluk, L., Rommelspacher, H. (eds) Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants. Current Topics in Neurotoxicity, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1542-8_4

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