A microdialysis profile of beta-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration

Abstract

Rationale: Alcohol stimulates the release of dopamine in the nucleus accumbens (NACB) of rats, mice and humans. There is evidence to suggest that the activation of beta-endorphin (beta-EP) in the mesolimbic pathway by alcohol and other drugs of abuse may be associated with the rise in dopamine levels in the NACB.

Objectives: The present studies investigate whether the release of beta-EP in the NACB is (1) dependent on the dose of alcohol that is administered, and (2) associated with changes in the extracellular concentrations of the catecholamines dopamine and norepinephrine, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the NACB.

Methods: Male Sprague-Dawley rats were implanted with a microdialysis probe positioned in the shell region of the NACB. Artificial cerebrospinal fluid was pumped at a rate of 2.3 microl/min in awake and freely moving animals and the dialysate was collected at 30-min intervals. After a baseline period, rats were injected intraperitoneally with either physiological saline or one of three doses of alcohol: 0.8, 1.6, or 2.4 g ethanol/kg body weight. The dialysates collected were analyzed with radioimmunoassay, to estimate the content of beta-EP; and high performance liquid chromatography, to estimate the content of dopamine, norepinephrine, DOPAC and HVA.

Results: Alcohol induced a dose-dependent increase in the extracellular levels of beta-EP and dopamine. However, elevations in the extracellular levels of norepinephrine, DOPAC and HVA did not reach significance. The largest increase in beta-EP and dopamine was observed with the 2.4 g/kg dose.

Conclusion: The alcohol-induced release of beta-EP and dopamine in the NACB is dose-dependent, where the highest dose resulted in more pronounced concentrations in the dialysate. Furthermore, the increase in the extracellular levels of dopamine appeared to occur at an earlier time point following alcohol administration, than for beta-EP. These results suggest that alcohol stimulates dopamine and beta-EP in the NACB, but probably does so via independent mechanisms.