Brain concentrations of biogenic amine metabolites in acutely treated and ethanol-dependent rats.

F Karoum, R J Wyatt, E Majchrowicz

Index: Br. J. Pharmacol. 56(4) , 403-11, (1976)

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Abstract

1 Mass fragmentography was used to measure whole brain concentrations of some of the major metabolites of tyramine, octopamine, dopamine and noradrenaline in acutely treated and in ethanol-dependent rats. 2 Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p-hydroxphenylacetic and p-hydroxymandelic acid (metabolites derived from tyramine and octopamine respectively). The effect on catecholamine metabolites was marked and therefore suggests that ethanol is selective in its effect on central metabolism of biogenic amines. 3 Acute ethanol treatment significantly increased brain concentration of homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Vanilmandelic acid (VMA) was not affected. All four metabolites (HVA, DOPAC, MHPG and VMA) were increased in the brains of rats rendered dependent on ethanol while still intoxicated (blood ethanol levels above 200 mg/dl). In ethanol-dependent rats undergoing ethanol withdrawal syndrome (no ethanol present in blood), the brain concentrations of HVA and DOPAC were normal while those of MHPG and VMA continued to be elevated. 4 From the decline in the concentrations of HVA and DOPAC after 50 mg pargyline/kg in control rats and rats acutely treated with ethanol, it was concluded that ethanol has no effect on the transport of phenolic acids across the blood brain barrier. 5 No reversal in the metabolism of catecholamines from an oxidative to a reductive pathway, analogous to that produced by ethanol in the periphery, could be established in the brain. 6 The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.