STRAIN-DEPENDENT EFFECTS OF DOPAMINE AGONISTS ON ACETYLCHOLINE-RELEASE IN THE HIPPOCAMPUS - AN IN-VIVO STUDY IN MICE

The effects of selective D-1 or D-2 dopamine receptor agonists and the indirect dopamine agonist cocaine on hippocampal acetylcholine releas e in mice of the C57BL/6 and DBA/2 inbred strains were investigated us ing intracerebral microdialysis. The D, SKF 38393 (10, 20, 30 mg/kg, i .p.), the D-2 agonist LY 171555 (0.5, 1, 2 mg/kg, i.p.) and cocaine (5 , 10, 15 mg/kg, i.p.) all increased, dose-dependently, acetylcholine r elease in the hippocampus of C57BL/6 mice. Both the D-1 agonist and co caine did not produce any significant effect in DBA/2 mice. In the lat ter strain, however, LY 171555 produced a decrease in acetylcholine re lease that was evident after 60 min from injection of the doses of 0.5 and 1 mg/kg, but not at the dose of 2 mg/kg. The effects observed in C57BL/6 mice as well as those produced by low doses of LY 171555 in th e DBA/2 strain were consistent with previous results obtained in rats. The present results indicate major strain-dependent differences in th e effects of dopamine agonists on hippocampal acetylcholine release in mice. Moreover, they suggest a complex genotype-related neural organi zation of dopamine-acetylcholine interactions in the mesolimbic system . Finally, the strain differences in the effects of the dopamine agoni sts on hippocampal acetylcholine release parallel previously reported strain differences in the effects of these substances on memory consol idation.