Role of genotype in brain dopamine metabolism and dopamine-dependent behavior of mice

Julia A. Skrinskaya, Ella M. Nikulina, Nina K. Popova

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

In mice of eight inbred strains-BALB/c, AKR/J, DBA/2, CBA, C57B1/6, DD, CC57Br, and C3H/He-brain dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in striatum and nucleus accumbens with tuberculum olfactorium, the structures of two main dopaminergic systems-nigrostriatal and mesolimbic-were determined. In both dopaminergic regions, no strain effect on either dopamine or DOPAC levels was found, while for HVA content a highly significant hereditary determination was shown. Influences of selective D1 and D2 dopamine receptor agonists-SK&F 38393 and quinpirole, respectively-as well as that of a mixed D1 D2 agonist, apomorphine, on general locomotor activity and stereotypic climbing were studied. By that, marked genotypic differences in dopamine-dependent behavior and dopamine receptor sensitivity were observed. Although both SK&F 38393 (5 mg/kg) and apomorphine (0.25 mg/kg) decreased locomotion, the effect being genotype dependent, in all strains of mice quinpirole (2.5 mg/kg) proved more potent in locomotor inhibition. SK&F 38393 (10 mg/kg) induced climbing, but 2.5 mg/kg apomorphine in most strains was much more effective. At the same time, quinpirole (up to 8 mg/kg) failed to induce this behavior. This suggests the crucial role of D1 receptors in the generation of climbing, attracting, at the same time, attention to the importance of D1 D2 interaction. The observed drastic interstrain differences in dopamine receptor sensitivity demonstrate the essential role of genotype in the effects of dopaminergic drugs.

Original languageEnglish (US)
Pages (from-to)261-267
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Volume42
Issue number2
DOIs
StatePublished - Jun 1992
Externally publishedYes

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Keywords

  • Brain dopamine metabolism
  • Climbing
  • D and D receptors
  • Inbred strains of mice
  • Locomotor activity

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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