Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-Chlorophenylpiperazine (mCPP) |
| |
Authors: | John H Krystal Elizabeth Webb Christian Grillon N Cooney Lisa Casal C A Morgan III Steven M Southwick Michael Davis Dennis S Charney |
| |
Institution: | (1) Department of Psychiatry, Yale University School of Medicine, Connecticut, USA, US;(2) VA-Yale Alcoholism Research Center and National Center for PTSD, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT 06516, USA, US;(3) Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06516, USA, US |
| |
Abstract: | Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated
the effects of intravenous infusion of the α2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.1 mg/kg), and placebo administered to 22 male patients meeting DSM-III-R criteria for alcohol
dependence and 13 male healthy subjects. Patients and healthy subjects completed 3 test days under double-blind conditions
in a randomized order. Patients were sober for 12–26 days prior to testing. On each test day, participants completed startle
testing 80 min following drug infusion. Stimuli with varying intensities (90, 96, 102, 108, 114 dB) were presented in a randomized
order balanced across four blocks. Stimuli consisted of 40-ms bursts of white noise administered every 45–60 s for 15–20 min
through headphones. Analyses indicated that patients exhibited elevated acoustic startle magnitudes on the placebo day relative
to healthy subjects. In patients, the magnitude of startle amplitudes elicited at 90 dB, but not 114 dB, correlated significantly
with the number of previous alcohol detoxifications. Yohimbine increased startle magnitudes and reduced startle latencies
relative to placebo and mCPP in both patients and healthy subjects. mCPP did not alter startle magnitude in either group.
Yohimbine also increased the probability that a 90-dB stimulus produced a startle response in healthy subjects, but not in
patients. Blunting of yohimbine effects on startle probability may reflect the baseline elevations in startle probability
levels in patients, but may also be consistent with other evidence of reduced postsynaptic, but not presynaptic, noradrenergic
function in these same patients. These data replicate and extend previous reports indicating that yohimbine facilitates the
acoustic startle response in humans. They also further implicate the number of episodes of ethanol withdrawal as a factor
influencing subsequent neurobiological responsivity in chronic alcoholic patients. Based on the current data, future research
should explore whether measurement of the acoustic startle response provides an objective quantitative severity measure of
ethanol withdrawal.
Received: 31 August 1995 /Final version: 4 October 1996 |
| |
Keywords: | Ethanol dependence Ethanol withdrawal Startle Noradrenaline Yohimbine Serotonin m-Chlorophenylpiperazine (mCPP) |
本文献已被 SpringerLink 等数据库收录! |
|