The effects of ethanol in combination with the α2-adrenoceptor agonist dexmedetomidine and the α2-adrenoceptor antagonist atipamezole on brain monoamine metabolites and motor performance of mice

Abstract

The time course of the effects of ethanol alone and in combination with the selective α₂-adrenoceptor agonist dexmedetomidine and the α-adrenoceptor antagonist atipamezole was studied in NIH-Swiss mice. Core body temperature, rotarod performance, motility and changes in the noradrenaline, dopamine, and 5-hydroxytryptamine (5-HT) metabolite contents of different brain parts (limbic forebrain, striatum, lower brainstem, the rest of the forebrain + midbrain and hypothalamus) were measured. Atipamezole (3 mg/kg) attenuated the hypothermia induced by either ethanol (3 g/kg) alone or ethanol in combination with dexmedetomidine (0.3 mg/kg). Atipamezole shortened the duration of the ethanol-impaired and ethanol + dexmedetomidine-impaired rotarod performance. Further, atipamezole prevented the decreased motility due to the combined treatment with ethanol and dexmedetomidine. Ethanol increased 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) values. Dexmedetomidine alone decreased MHPG and 5-hydroxyindoleacetic acid (5-HIAA) concentrations and increased DOPAC and HVA values. Dexmedetomidine combined with ethanol resulted in a further increase in DOPAC and HVA values. Pharmacokinetic parameters did not contribute to this antagonism of ethanol's effects by atipamezole, nor did the antagonism observed in rotarod performance or hypothermia seem to correlate with the changes seen in the brain noradrenaline and dopamine or 5-HT metabolism. In conclusion, these findings suggest that several ethanol effects are not mediated via direct activation of α₂-adrenoceptors, even though some of ethanol's behavioral and physiological effects may be antagonized by coadministration of α₂-adrenoceptor antagonists.