Fewer pigmented neurons in the locus coeruleus of uncomplicated alcoholics

Abstract

Altered noradrenergic function is associated with alcoholism. Reduced brain norepinephrine (NE) concentrations and beta-adrenergic receptor supersensitivity following chronic alcohol consumption suggest a reduced level of noradrenergic neurotransmission. To further elucidate the reason for changes in noradrenergic function, we determined the number of melanin-containing noradrenergic neurons in the locus coeruleus (LC) postmortem from 11 controls and 7 alcoholics. Controls did not have a known history of psychiatric or neurologic disorders and were drug-free by toxicological screen. The diagnosis of alcohol-dependence was based on DSM-III-R criteria. Alcoholics differed from controls in having 23% fewer LC neurons (control: 43,472 +/- 1,021; alcoholic: 33,398 +/- 2184; P < 0.0005) and 46% lower density of neurons (control: 1,227 +/- 89 cells per mm3; alcoholic: 663 +/- 94 cells per mm3; P = 0.001). The reduction in neurons was bilateral and throughout the middle third of the LC. The two groups did not differ with respect to LC length (control: 16.1 +/- 0.6 mm; alcoholic 15.3 +/- 0.9 mm; P = 0.47) or total LC volume (control: 37.3 +/- 2.8 mm3; alcoholic: 46.5 +/- 4.2 mm3; P = 0.09). Changes in noradrenergic neurotransmission in alcoholics may be due to fewer noradrenergic neurons in the locus coeruleus and may contribute to memory loss and depression, common consequences of alcoholism.