GABA-mediated dopaminergic modulation associated with the different anesthetic sensitivity between ddN and C57BL mice

We investigated the differences of the GABAergic and the dopaminergic response to anesthetics in ddN and C57BL mice which have different anesthetic sensitivity. The locomotor activity of the two strains of mice was measured during 30 minutes after midazolam administration (20 mg/kg, intraperitoneally) and serum midazolam concentration was measured by high performance liquid chromatography. Prosencephalic and mesencephalic dopamine concentration was also measured by using homoginized brain tissue after midazolam administrations. The ddN mice were more active than BL mice after midazolam administration, nevertheless serum midazolam concentration was higher than that of BL mice. There was significant difference in prosencephalic dopamine concentration between ddN and BL mice. It was shown that midazolam increased prosencephalic dopamine concentration but did not affect that in BL mice. Because midazolam acts on the GABA_A receptor, the increase in prosencephalic dopamine concentration was elicited by GABA-mediated modulation of the dopaminergic system. It is concluded that the mechanism of different anesthetic sensitivity between ddN and BL mice may be associated with GABA-mediated dopaminergic modulation.