Brain Concentrations of Biogenic Amine Metabolites in Acutely Treated and Ethanol‐dependent Rats

Abstract

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 ethanoldependent rats. Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p‐hydroxyphenylacetic 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. 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. 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. 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. The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.

Ethanol-Induced c-Fos Expression in Catecholamine- and Neuropeptide Y-Producing Neurons in Rat Brainstem

“…Consistent with the present results, acute administration of ethanol has been found to increase synthesis, turnover, and release of NE, which suggests an important role for this catecholamine in regulating the neurobiological effects of ethanol (Carlsson and Lindqvist, 1973;Corrodi et al, 1966;Hunt and Majchrowicz, 1974;Karoum et al, 1976;Pohorecky and Jaffe, 1975). Although chemical-induced lesions of NE-producing cells have produced conflicting results (Kiianmaa, 1980;Melchior and Myers, 1976;Myers and Melchior, 1975;Richardson and Novakovski, 1978), blocking conversion of dopamine to NE with dopamine ␤-hydroxylase inhibitors has been found to reduce ethanol consumption in rats (Brown et al, 1977), and infusion of NE into the paraventricular nucleus of the hypothalamus (PVN) has been found to increase ethanol consumption in rats (Hodge et al, 1996).…”

“…Previous research has indicated that the catecholamine norepinephrine (NE) may be involved in regulating voluntary ethanol ingestion and the intoxicating effects that are produced by this drug (Brown et al, 1977;Hodge et al, 1996;Lister et al, 1989;Mao and Abdel-Rahman, 1996). Additionally, ethanol administration has been found to increase synthesis, turnover, and release of NE (Carlsson and Lindqvist, 1973;Corrodi et al, 1966;Hunt and Majchrowicz, 1974;Karoum et al, 1976;Pohorecky and Jaffe, 1975), and ethanol induces cFLI in brainstem regions known to be populated by catecholaminergic cells (i.e., the LC, ventrolateral medulla [VLM], and NTS) (Cunningham and Sawchenko, 1988;Palkovits et al, 1992;Riche et al, 1990;Gray, 1990, 1995). Therefore, we assessed coexpression of cFLI with tyrosine hydroxylase (TH) (the rate-limiting enzyme in catecholamine biosynthesis) in the brainstem.…”

There and Back Again: A Tale of Norepinephrine and Drug Addiction

“…For example, acute administration of ethanol modulates the synthesis, turnover, and release of central NE (Corrodi et al, 1966;Carlsson and Lindqvist, 1973;Hunt and Majchrowicz, 1974;Pohorecky and Jaffe, 1975;Karoum et al, 1976), and the activity of noradrenergic neurons (Aston- Jones et al, 1982;Pohorecky and Brick, 1988;Verbanck et al, 1990). Moreover, ethanol has a greater effect on NE turnover and release than on DA (Corrodi et al, 1966;Hunt and Majchrowicz, 1974).…”

Effects of ethanol on catecholamine levels and related enzyme activities in different brain regions of rats.

“…Table 1 and Fig. 1 (11,12) or an increase in a release of NE (13). Simultaneous assay of DBH activity, however, revealed that its activity tended to decrease in this region.…”