Effect of parachlorophenylalanine, an inhibitor of the serotonin synthesis enzyme, on the brain dopamine system of cataleptic mice

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Abstract

This study examined the effects of administration of parachlorophenylalanine (PCPA), an inhibitor of the key enzyme serotonin synthesis, on the freezing immobility and dopamine brain system in CBA/Lac mice with a hereditary predisposition to catalepsy. Administration of PCPA (300 mg/kg/day, 3 days) did not affect the duration of cataleptic freezing. Whereas, dopamine content decreased in the hypothalamus and midbrain and increased in the striatum and nucleus accumbens of mice after PCPA treatment. The administration of the drug did not affect the levels of DOPAC and HVA (dopamine metabolites) in the all studied brain structures. In addition, a PCPA-induced increase in the mRNA level of DRD2 receptor gene in the midbrain and Comt (catechol-O-methyltransferase) gene in the hypothalamus and midbrain were found. However, no effect of PCPA on the expression of DRD1 receptor gene and Th (tyrosine hydroxylase, key enzyme dopamine synthesis) gene in the brain was found. Thus, inhibition of the key enzyme of 5-HT synthesis had a significant effect on the brain DA system of CBA/Lac mice, with the greatest changes being found in the midbrain and hypothalamus.

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About the authors

D. V. Bazovkina

Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences

Author for correspondence.
Email: daryabazovkina@gmail.com
Russian Federation, Novosibirsk

E. Yu. Bazhenova

Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences

Email: daryabazovkina@gmail.com
Russian Federation, Novosibirsk

A. V. Kulikov

Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences

Email: daryabazovkina@gmail.com
Russian Federation, Novosibirsk

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2. Fig. 1. Effect of parachlorophenylalanine administration (300 mg/kg, 3 days) on the levels of dopamine (a), its metabolites DOPAC (b), HVA (c) and the dopamine metabolism index (DOPAC+HVA/dopamine) (d) in the brain structures of CBA mice. *p < 0.05, **p < 0.01. N = 10 animals per group.

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3. Fig. 2. Effect of parachlorophenylalanine administration (300 mg/kg, 3 days) on the expression of dopamine receptor genes Drd1 (a), Drd2 (b), catechol-O-methyltransferase gene Comt (dopamine metabolism enzyme) (c) and tyrosine hydroxylase gene Th (dopamine synthesis enzyme) (d) in the brain structures of CBA mice. Gene expression is presented as the ratio of the amount of cDNA of the studied genes to 100 copies of Polr2a cDNA. *p < 0.05, **p < 0.01. N = 10 animals per group.

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