Role of genotype in brain dopamine metabolism and dopamine-dependent behavior of mice.
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.
Skrinskaya
J A
JA
Behavioral Phenogenetics Laboratory, Siberian Branch of the Academy of Sciences of Russia, Novosibirsk, Russia.
Nikulina
E M
EM
Popova
N K
NK
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D005838:Genotype; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013045:Species Specificity; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine