THE EFFECTS OF ETHANOL IN COMBINATION WITH THE ALPHA(2)-ADRENOCEPTOR AGONIST DEXMEDETOMIDINE AND THE ALPHA(2)-ADRENOCEPTOR ANTAGONIST ATIPAMEZOLE ON BRAIN MONOAMINE METABOLITES AND MOTOR-PERFORMANCE OF MICE

The time course of the effects of ethanol alone and in combination wit h the selective alpha(2)-adrenoceptor agonist dexmedetomidine and the alpha-adrenoceptor antagonist atipamezole was studied in NIH-Swiss mic e. Core body temperature, rotarod performance, motility and changes in the noradrenaline, dopamine, and 5-hydroxytryptamine (5-HT) metabolit e contents of different brain parts (limbic forebrain, striatum, lower brainstem, the rest of the forebrain + midbrain and hypothalamus) wer e measured. Atipamezole (3 mg/kg) attenuated the hypothermia induced b y either ethanol (3 g/kg) alone or ethanol in combination with dexmede tomidine (0.3 mg/kg). Atipamezole shortened the duration of the ethano l-impaired and ethanol + dexmedetomidine-impaired rotarod performance. Further, atipamezole prevented the decreased motility due to the comb ined treatment with ethanol and dexmedetomidine. Ethanol increased 3-m ethoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) values. Dexmedetomidine alo ne decreased MHPG and 5-hydroxyindoleacetic acid (5-HIAA) concentratio ns and increased DOPAC and HVA values. Dexmedetomidine combined with e thanol resulted in a further increase in DOPAC and HVA values. Pharmac okinetic parameters did not contribute to this antagonism of ethanol's effects by atipamezole, nor did the antagonism observed in rotarod pe rformance or hypothermia seem to correlate with the changes seen in th e brain noradrenaline and dopamine or 5-HT metabolism. In conclusion, these findings suggest that several ethanol effects are not mediated v ia direct activation of alpha(2)-adrenoceptors, even though some of et hanol's behavioral and physiological effects may be antagonized by coa dministration of alpha(2)-adrenoceptor antagonists.