Eye Movement Effects of Diazepam in Sons of Alcoholic Fathers and Male Control Subjects

Abstract

Both animal and human studies suggest that the GABA-benzodiazepine receptor complex may be involved in the acute effects of ethanol, as well as the development of tolerance and dependence with chronic ethanol use. The current study was performed to assess sensitivity to benzodiazepines, and thus the functional sensitivity of the GABA-benzodiazepine receptor system, in subjects at high risk for alcoholism. Sons of alcoholic fathers (SOAs; n = 27) were compared with male controls without a family history of alcoholism (n = 23) in response to diazepam versus placebo. SOAs and controls received four logarithmically increasing doses of intravenous diazepam or placebo in randomized order on 2 days at least 1 week apart. Effects of diazepam were assessed using two eye movement tasks, peak saccadic eye movement velocity, and average smooth pursuit eye movement gain, which provide reliable, quantitative measures of benzodiazepine effects. In addition, memory, self-rated sedation, and pleasurable drug effects were measured. In comparison with control subjects, SOAs displayed significantly less diazepam effects on peak saccade velocity, average smooth pursuit gain, memory, and self-rated sedation, but significantly greater pleasurable drug effects. Differences in response to diazepam between SOAs and male controls may reflect altered functional sensitivity of the central GABA-benzodiazepine receptor system or a more general difference between groups in the effects of CNS active or sedating drugs.

Smooth Pursuit Eye Movement Dysfunction in Substance-Dependent Patients: Mediating Effects of Antisocial Personality Disorder

“…A family history of alcoholism has been associated with SPEM impairment in both healthy volunteers [50] and cocaine abusers [18]. A reanalysis of the results of the present study, replicating the analysis design used by Bauer [18], did reveal a significant effect of a paternal history of alcoholism on SPEM in cocaine-dependent patients, thereby replicating Bauer's finding.…”

Increased sensitivity to alprazolam in females with a paternal history of alcoholism

“…Other studies failed to observe differences between FHP and FHN males following diazepam administration (de Wit 1991;Schuckit et al 1991). In contrast, Cowley et al (1992Cowley et al ( , 1994 found that FHP males were less sensitive to the memory and sedating effects of intravenous diazepam, but reported more positive subjective effects than FHN males. Two other studies that used imaging techniques provide additional evidence that the neurophysiological effects of benzodiazepines are different in FHP than in FHN individuals (Volkow et al 1995;Streeter et 158 indicated that there was a significant drug × group effect for "heaviness in limbs" (F 1,26 =4.54, P<0.04).…”

“…Cowley et al (1992Cowley et al ( , 1994 reported that sons of alcoholics were less sensitive to some of the "negative" effects of diazepam (sedation, impaired memory), but more sensitive to some of the "positive" subjective effects of diazepam than normal controls. While several studies comparing FHP and FHN males (de Wit 1991;Schuckit et al 1991) failed to show any differences following diazepam, Ciraulo et al (1989) found that FHP males reported more euphoria following alprazolam than FHN males, whereas buspirone did not increase ratings of euphoria in FHP males.…”

Saccade and cognitive impairment associated with kava intoxication

“…The saccadic slowing was characterized by a reduced peak velocity of visually guided saccades, although the latency of visually guided saccades was not affected by kava intoxication nor was their duration. Saccade peak velocity is sensitive to the acute effects of sedating drugs including benzodiazepines, barbiturates, anticonvulsants and alcohol and is considered a valuable indicator of the pharmacological effects mediated by the GABA-benzodiazepine receptor complex (Jürgens et al, 1981;Thurston et al, 1984;Richens et al, 1993;Cowley et al, 1994;Kroboth et al, 1998;Moser et al, 1998). An interaction between kava lactones and GABAergic systems is well established in animal studies that show kava lactones cause alterations to the GABA-benzodiazepine receptor complex through their direct actions on sodium-dependent ion channels (Duffield and Jamieson, 1988;Davies et al, 1992;Jussofie et al, 1994;see Cairney et al, 2002 for review).…”