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Abstract
The present study was performed in order to establish, with a simple and safe neuroendocrinological test, whether alcoholism is associated with alterations in sensitivity to benzodiazepines. For this purpose, we tested the stimulatory effects of diazepam on GH secretion. An intravenous bolus of 10 mg diazepam was injected in 51 (33-51-year-old) alcoholic men after at least 5 weeks of abstinence and in 20 age- and weight-matched normal controls. On a different occasion, a control test with placebo (physiological saline) was performed in the same subjects. Diazepam but not placebo administration induced a striking increase of GH secretion in the normal controls. In contrast, neither diazepam nor placebo treatment significantly changed the basal serum GH levels in alcoholic men. These data show that alcoholism is associated with disrupted benzodiazepine activity on the hypothalamic-pituitary control of GH secretion. The simplicity of the diazepam GH-releasing test makes the drug suitable for clinical research in alcoholism.
Introduction
Alcohol and benzodiazepines often have been considered together because the effects of these drugs show various clinical and neurological correlates. In fact, alcohol dependence is very frequent in high-dose benzodiazepine regular users1 and benzodiazepines (particularly intermediate activity preparations, such as chlordiazepoxide and diazepam) show cross-tolerance and dependence with alcohol.2,3 Furthermore, withdrawal from alcohol or benzodiazepines is often associated with similar somatic symptoms4 and benzodiazepines (particularly chlordiazepoxide and diazepam) are the drugs of choice for the management of alcohol withdrawal.2,5 Studies of rat brain in vitro have shown regional differences in the densities and/or affinities of benzodiazepine recognition sites and in the coupling between GABA and benzodiazepine binding sites between alcohol-preferring and nonpreferring rats.6 In addition, differences in the effects of lorazepam on regional brain glucose metabolism have been described recently in subjects at risk for alcoholism by Volkow and coworkers7 with positron emission tomography and 2-deoxy 2 (18F) fluoro-D-glucose in subjects with positive or negative family history for alcoholism.7 These studies suggested that a disruption in the activity of benzodiazepine might affect the alcoholic brain. The present study was undertaken in order to confirm the disorder affecting benzodiazepine activity in alcoholics from a neuroendocrine point of view and to develop an easy method for the study of this phenomenon. In view of the well-known growth hormone(GH)releasing action of...