Startle response during smoking and 24 h after withdrawal predicts successful smoking cessation

RATIONALE: The startle response is thought to reflect changes in attentional processes in humans. The startle response shows a number of forms of plasticity, of which prepulse inhibition (PPI) refers to the attenuation of the startle response to a strong sensory stimulus (pulse), when such a pulse is preceded by a stimulus of lower intensity (prepulse). Recent studies have shown that nicotine modulates startle and PPI of the startle reflex in humans and animals. The present study examined individual differences in cognitive benefits obtained from smoking as indexed by startle response and PPI. OBJECTIVES: We investigated, using a within-subjects design, the effects of cigarette smoking via a comparison of baseline and withdrawal measures of startle and PPI in 18 subjects wishing to quit cigarette smoking. The relapse of five of these subjects enabled a between-group comparison of these measures with the successful quitters. METHODS: Startle and PPI were measured on three separate occasions: before quitting, 24 h after quitting and 1 month after quitting. RESULTS: The presence of a high startle response amplitude while subjects were still engaged in their normal smoking patterns (baseline) and the occurrence of a significant drop of startle amplitude in withdrawal relative to baseline factors were found to be predictive of an individual's ability to quit smoking. Changes in PPI were found to reflect these changes in startle amplitude. CONCLUSIONS: The observed response patterns are discussed in terms of individual differences in commitment to quitting and self-dosing to manipulate attentional mechanisms as measured by the acoustic startle response. Furthermore, it is suggested that these specific response profiles may be predictive of the ability to quit smoking.     

Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia

The prevalence of tobacco smoking is known to be higher in patients with schizophrenia than other psychiatric disorders and general population. These patients also show reduced prepulse inhibition (PPI) of the startle response. PPI refers to a reduction in response to a strong startling stimulus if preceded shortly by a stimulus of sub-threshold intensity. PPI is thought of as an objective index of sensorimotor gating. Nicotine administered subcutaneously or via cigarette smoking enhances PPI in healthy human beings. It also enhances PPI at low, but not high, doses in the rat. We examined the influence of smoking on PPI of the acoustic startle response in 46 male patients with chronic schizophrenia. In a naturalistic design, patients (n = 9) who smoked a cigarette less than 10 min prior to being tested on PPI were compared with other smoking (n = 23) and non-smoking patients (n = 14). We found that the group of patients who smoked a cigarette prior to being tested had significantly greater PPI than other two groups. These observations suggest a PPI-enhancing effect of cigarette smoking on PPI in patents with schizophrenia. Higher prevalence of cigarette smoking in schizophrenic patients may reflect an attempt to improve sensorimotor gating deficits. Copyright 2001 John Wiley & Sons, Ltd.     

Smoking withdrawal, nicotine dependence and prepulse inhibition of the acoustic startle reflex

The present study examined the relationship between nicotine dependence as measured by the Fagerstrom Tolerance Questionnaire (FTQ) and prepulse inhibition (PPI) of the acoustic startle reflex measured after overnight smoking withdrawal in a non-clinical population of male smokers with no history of psychiatric disorders or drug/alcohol abuse. It was found that smokers who scored high (>median) on the FTQ showed significantly less PPI as compared to those scoring low (<median) on this scale. This finding further supports a role for nicotine in modulation of PPI, as has previously been found in rats and also in human beings. Received: 26 November 1997/Final version: 8 June 1998     

Effects of haloperidol, clozapine, and quetiapine on sensorimotor gating in a genetic model of reduced NMDA receptor function

Rationale Reduced N-methyl d-aspartate (NMDA) receptor function is hypothesized to contribute to the pathophysiology of schizophrenia. In order to model chronic and developmental NMDA receptor hypofunction, a mouse line was developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor. These mice show increased acoustic startle reactivity and deficits in prepulse inhibition (PPI) of acoustic startle. Objectives The present study tested the hypothesis that these altered acoustic startle responses in the NR1 hypomorphic (NR1−/−) mice would be affected by antipsychotic drug treatment. Methods Mice were injected with drugs 30 min before assessment of acoustic startle responses with and without prepulse stimuli. Results Haloperidol (0.5 or 1.0 mg/kg) did not reduce the increased startle reactivity in the NR1−/− mice, but did increase PPI in both the mutant and wild type mice. Clozapine (3 mg/kg) and quetiapine (20 mg/kg) reduced startle magnitude and increased PPI in both the wild type and mutant mice. The antidepressant drug imipramine (10 and 20 mg/kg) had minimal effects on startle amplitude in NR1−/− or wild type mice. However, for the 20-mg/kg dose of imipramine, a significant increase in PPI was observed in the wild type animals, but not in the mutant mice. Conclusions The results demonstrate that PPI can be increased in a mouse model of chronic NMDA receptor hypofunction by typical and atypical antipsychotic drugs. The similar effects of typical and atypical antipsychotic drugs to increase PPI in the wild type and mutant mice indicates that the assessment of behavior of the NR1 hypomorphic mice in the PPI paradigm offers no advantage over the wild type controls for identifying new clozapine-like drugs.     

Differential effects of apomorphine on prepulse inhibition of acoustic startle reflex in two rat strains

Apomorphine disruption of prepulse inhibition (PPI) has been proposed as an animal model of sensorimotor gating deficits exhibited by schizophrenics. The effects of apomorphine on PPI of the acoustic startle reflex in male rats of Wistar and CD (Sprague-Dawley derived) strains were compared under identical test conditions. In Wistar rats, subcutaneous administration of 0.25–1.0 mg/kg apomorphine blocked PPI without affecting startle amplitude. In CD rats, apomorphine (0.3–3.0 mg/kg, SC) had no effect on PPI, but increased startle amplitude. Therefore, choice of rat strain is an important factor in the design of experiments studying apomorphine effects on PPI.     

The effects of smoking on acoustic prepulse inhibition in healthy men and women

Acoustic prepulse inhibition (PPI) refers to the reduction of the startle reflex to an intense stimulus if it is preceded by a weak stimulus. Nicotine and smoking have been reported to enhance PPI in rats and in healthy men, respectively. We studied the influence of smoking on PPI in healthy men and women, comparing non-smokers, deprived smokers, and smokers smoking during the test session after deprivation or after ad libitum smoking. Smoking during the session enhanced PPI, without affecting startle reaction or habituation over time. In addition, the effect of smoking on PPI was gender dependent. In men, ad libitum smoking enhanced PPI compared with non-smokers, while, in women, deprivation reduced PPI and smoking restored PPI to the level of non-smokers. Received: 24 July 1997/Final version: 19 November 1997     

Caffeine and prepulse inhibition of the acoustic startle reflex

Rationale: A stimulus presented immediately prior to a startle reflex-eliciting stimulus inhibits the startle reflex. This is termed prepulse inhibition (PPI) and is postulated to index automatic and controlled attentional processing of the prepulse. Objective: Two experiments investigated the effect of 0, 2, and 4 mg/kg oral caffeine on PPI of the acoustic startle eyeblink reflex across stimulus onset asynchronies (SOAs) ranging from 30 to 420 ms. In experiment 1, acoustic prepulses were used and automatic attention was investigated, whereas in experiment 2, acoustic and tactile prepulses were used and automatic and controlled attention was investigated. Controlled attention was investigated by instructing the subjects to attend to one stimulus (attended stimulus) and not to another stimulus (non-attended stimulus). Methods: Caffeine was administrated to human subjects in within-subjects designs (n=24 and n=18). Startle reflexes to 100 dB noise were recorded by electromyography. A mood scale and readings of blood pressure indexed arousal. Results: Caffeine increased the indexes of arousal. There were, however, no significant main effects of caffeine on startle, nor did caffeine significantly interact with any other variable. Attended acoustic prepulses increased PPI at the 120 ms and longer SOAs. Caffeine 4 mg/kg abolished this difference between attended and non-attended stimuli. Attended tactile prepulses facilitated startle at short SOAs, and caffeine reduced facilitation of startle by tactile prepulses. Conclusions: Caffeine did not facilitate automatic attention. Caffeine 4 mg/kg abolished the effect of controlled attention on PPI. Facilitation of startle by attended acoustic prepulses is best explained by facilitation of motoneurons in the facial nucleus. Received: 11 May 1999 / Final version: 1 July 1999     

Effects of smoking on acoustic startle and prepulse inhibition in humans

RATIONALE: Prepulse inhibition of the acoustic startle response (PPI) is a paradigm in which a startle response to an auditory stimulus is reduced when that stimulus is preceded by a lower intensity, non-startling stimulus (prepulse). PPI is used as an operational measure of sensorimotor gating in both humans and other mammals. Acute administration of nicotine enhances PPI in rats, an effect that has been recently demonstrated in humans. OBJECTIVES: We compared PPI in 12 male smokers and 14 male non-smokers tested in four repeat startle sessions across 2 test days in order to examine further the effects of smoking and smoking withdrawal on acoustic startle and PPI. METHODS: In a crossover design, the smokers smoked ad lib or abstained from smoking overnight prior to 9 a.m. testing. These 2 test days were in randomized order. On both days, smokers were immediately retested after smoking three cigarettes. Non-smokers were tested twice on each of 2 separate days. RESULTS: Across sessions, the smokers had reduced startle to pulse alone stimuli in the first block of each session when compared to the non-smokers. The non-smokers had no change in gating across their four test sessions. For the smokers, the abstinence condition produced a non-significant reduction in PPI compared to that of the ad lib smoking day. During the smoking abstinence session, smokers had comparable gating to non-smokers. Smoking immediately after washout produced a significant improvement in PPI such that gating in the smokers exceeded that of the non-smokers. CONCLUSION: Smoking after overnight washout from cigarettes enhanced sensorimotor gating compared to pre-smoking values and compared to gating in non-smokers.     

Sex differences in sensorimotor gating of the human startle reflex: all smoke?

Rationale: A recent report described sex differences in the effects of nicotine use and withdrawal on prepulse inhibition of acoustic startle (PPI), but no sex differences in PPI in non-smokers. Objective: To determine whether previously reported male>female acoustic PPI reflect sex differences in smoking effects on PPI, rather than simple sex differences in the regulation of PPI. A retrospective analyses of >600 carefully screened normals tested over the past 12 years was completed. Results: Male>female acoustic PPI was detected in analyses that included: 1) all subjects; or 2) self-declared non-smokers. Conclusions: Sex differences in PPI cannot be accounted for by smoking history, because they are present across a large sample of non-smoking normal controls. Received: 28 January 1999 / Final version: 28 June 1999     

The effects of smoking high nicotine cigarettes on prepulse inhibition, startle latency, and subjective responses

RATIONALE: Several previous investigations with animals and humans have suggested that nicotine enhances prepulse inhibition of the startle reflex (PPI). However, the administration of nicotine activates mesolimbic dopamine, and activation of mesolimbic dopamine is known to attenuate prepulse inhibition of the startle reflex (PPI), which might suggest that nicotine would decrease PPI. OBJECTIVE: The primary aim of this study was to test rigorously the effects of smoking high nicotine cigarettes on PPI and other measures (e.g., heart rate, craving, and mood) when the concentration of nicotine peaks in the brain (i.e., immediately after smoking). METHODS: Thirty smokers participated in two experimental sessions 1 week apart. Two high nicotine cigarettes were smoked in one session, and two control cigarettes were smoked in the other session after overnight deprivation. RESULTS: The results indicated that smoking the high nicotine cigarettes decreased PPI and that PPI increased across trials in both conditions. The interaction between nicotine dose and trial was not significant, although it appeared that high nicotine may have reversed an increase in PPI across trials in the control condition. High nicotine cigarettes also significantly increased heart rate, decreased the latency to peak startle response on control trials, but did not alter the magnitude of the startle response. DISCUSSION: The findings suggest that either high nicotine cigarettes reduced PPI, or possibly, that high nicotine cigarettes may have reversed an increase in PPI across trials as evident in the control condition.     

Disruption of the prepulse inhibition of the startle reflex in vasopressin V1b receptor knockout mice: reversal by antipsychotic drugs.

In the present study, we investigated whether mice lacking the arginine vasopressin (AVP) V1b receptor (V1bR) exhibit deficits of prepulse inhibition (PPI) of the startle reflex, reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. V1bR knockout (KO) mice displayed significantly reduced levels of PPI of the startle reflex. In addition to PPI deficits, V1bR KO mice showed increased acoustic startle response. However, acoustic startle response was not significantly correlated to the PPI of the startle reflex in V1bR KO mice. V1bR KO mice also showed a decrease in basal levels of extracellular dopamine (DA) in the medial prefrontal cortex, which is thought to be an important brain region for PPI. Moreover, PPI deficits observed in the V1bR KO mice are significantly reversed by atypical antipsychotics such as risperidone and clozapine but not by a typical neuroleptic haloperidol, like in schizophrenic patients. By contrast, we did not observe any significant differences between V1bR KO mice and wild-type mice in the open-field, light/dark, elevated plus maze, and forced swimming tests. The results of the present study indicate that V1bR may be involved in the regulation of PPI of the startle reflex. The V1bR has been considered an important molecular target for the development of antipsychotic drugs.     

Potentiation of prepulse inhibition of the startle reflex in rats: pharmacological evaluation of the procedure as a model for detecting antipsychotic activity

Prepulse inhibition (PPI) of the startle reflex – whereby presentation of a weak prepulse preceding a startling pulse diminishes the amplitude of the startle reflex – is disrupted by dopamine (DA) agonists; this disruption can be reversed by antipsychotics. There are also some indications in the literature that a few antipsychotics (most notably clozapine and haloperidol) may, on their own, have effects opposite to those of DA agonists, i.e. may enhance PPI. In order to explore these antipsychotic-induced potentiations of PPI more thoroughly, we assessed, in Sprague-Dawley rats, the effects of IP administration of various clinically effective antipsychotics in a PPI procedure with levels of PPI (ranging from 5 to about 40%) low enough to facilitate detection of PPI-potentiating effects of drugs. Both clozapine (5–20 mg/kg) and haloperidol (0.25–1 mg/kg) robustly and dose-dependently potentiated PPI. A similar effect was not seen with risperidone (0.1–1 mg/kg) or with the three substituted benzamides amisulpride (10–60 mg/kg), raclopride (0.1–3 mg/kg) and remoxipride (1–10 mg/kg). As risperidone is known to have prominent 5-HT₂ antagonistic activity, these results do not indicate a role for 5-HT₂ receptors in the clozapine and haloperidol PPI-enhancing effects. The absence of effects with the benzamides and with risperidone, at doses with known anti-dopaminergic activity, suggests that DA antagonist activity is not involved. The demonstration that prazosin (3–20 mg/kg), a non-antipsychotic with α₁ adrenoceptor antagonistic properties, dose-dependently potentiated PPI indicates that α₁ receptors might mediate the clozapine and haloperidol PPI-enhancing activity. Additionally, the finding that diazepam (1–10 mg/kg) did not enhance, but on the contrary reduced PPI, argues against a sedation- or general depressant-mediated effect of clozapine, haloperidol and prazosin. The negative results with four clinically active antipsychotics (risperidone and the benzamides), and the positive result with the non-antipsychotic prazosin, indicate that this PPI-enhancing procedure has poor predictive validity as a screening tool for potential antipsychotics. Received: 14 November 1996/Final version: 6 February 1997     

Hippocampal modulation of acoustic startle and prepulse inhibition in the rat.

Prepulse inhibition (PPI) is the normal reduction in a startle response that occurs when the startling stimulus is preceded by a weak lead stimulus ("prepulse"). Schizophrenic patients exhibit abnormally low levels of PPI; therefore, animal models of deficient PPI may provide information regarding neural dysfunctions underlying schizophrenia. We recently reported that infusion of the cholinergic agonist carbachol into the dentate gyrus (DG) disrupts PPI in the rat. We now report the effects of carbachol microinjected into CA1, the DG, or the ventral subiculum (VS) on acoustic startle and PPI. Carbachol infusion into CA1 or the DG depressed startle. Carbachol infusion decreased PPI with a regional rank-order potency CA1 > DG > VS. CA1 infusions more potently depressed the startle reflex. By contrast, DG infusions preferentially decreased PPI, while VS infusions decreased PPI without altering startle amplitude. Coinfusion with the muscarinic cholinergic antagonist atropine opposed the effects of carbachol. These results demonstrate the regional heterogeneity and pharmacological specificity of the hippocampal cholinergic modulation of acoustic startle and PPI and suggest that abnormalities within various regions of the hippocampal formation may contribute to deficient sensorimotor gating in schizophrenic patients.     

Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating

Oxytocin plays an important role in the regulation of normal cognitive functions and behaviors, which are disturbed in schizophrenia. Several studies suggest that oxytocinergic function is abnormal in schizophrenia patients. Thus, oxytocin may be involved in the pathophysiology associated with this disorder. This study investigated the regulatory effects of oxytocin on deficits in prepulse inhibition (PPI) associated with schizophrenia. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating which can be measured across many species. PPI is the normal suppression of the startle reflex when the intense startling stimulus (“pulse”) is immediately preceded by a weaker stimulus (“prepulse”). Subcutaneously administered oxytocin (0.04–1.0 mg/kg) dose-dependently restored PPI that had been reduced in rats by dizocilpine, a non-competitive NMDA antagonist, and by amphetamine, an indirect dopamine agonist. Oxytocin did not produce a significant effect on baseline PPI or PPI decreased by the direct dopamine agonist, apomorphine. The underlying startle response amplitude was also not significantly altered by oxytocin. These results suggest that oxytocin may play an important role in the modulation of dopaminergic and glutamatergic regulation of PPI, and that it may act as a novel endogenous antipsychotic. Received: 26 March 1998/Final version: 11 May 1998     

Effects of caffeine on sensorimotor gating of the startle reflex in normal control subjects: impact of caffeine intake and withdrawal

RATIONALE: Prepulse inhibition (PPI), a cross-species measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. This study was designed to assess caffeine effects on PPI in normal humans, as part of an effort to understand cross-species differences and similarities in the neurochemical regulation of PPI. METHODS: Startle was measured during a screening session; 7 days later, subjects were retested after placebo or caffeine (200 mg; double-blind design). Subjects were characterized as low versus high caffeine drinkers based on established scales (range 11-628 mg/day), and either maintained ad libitum caffeine intake (Ad lib study; n=18) or refrained from caffeine consumption for > or =15 h prior to testing (Withdrawal study; n=12). Autonomic and self-rating measures, acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in divided sessions for 3 h post-treatment. RESULTS: There were significant effects of caffeine and/or caffeine withdrawal on several self-rating and autonomic measures, and on startle reflex habituation, but not on acoustic or tactile startle magnitude or PPI. Difference scores of startle data from screening versus test days revealed no group effects on startle magnitude, but PPI difference scores revealed that caffeine had opposite effects on low versus high caffeine drinkers (means=57 versus 258 mg/day) in the two withdrawal states. In the absence of withdrawal, caffeine reduced PPI in heavy caffeine drinkers; during withdrawal, caffeine increased PPI in heavy caffeine drinkers. The opposite pattern was evident in low caffeine drinkers. CONCLUSIONS: While a physiologically active dose of caffeine has no simple effects on PPI in normal humans, both withdrawal states and normal levels of caffeine consumption may be important factors in understanding this drug's effects on sensorimotor gating.     

Lipopolysaccharide reduces tactile startle response magnitude but not prepulse inhibition in rats: A dose-response examination

As a result of innate immune system stimulation, lipopolysaccharide (LPS) exposure produces a range of behavioral modifications referred to as “sickness behaviors.” This study assessed the effects of multiple doses of LPS on air-puff tactile startle reflex (Startle-Only trials) and acoustic prepulse inhibition (PPI) in adult male rats. Rats were injected intraperitoneally with LPS (300, 200, 100, or 50 μg/kg LPS, n = 9, 10, 10, and 10 respectively) or saline vehicle (n = 10) on 2 test days 72 h apart. Magnitude of the startle response was recorded following 15 psi air-puffs (Startle-Only trials) and auditory PPI of the tactile startle response (with prepulses at + 3, + 6 and + 12 dB above background noise). Startle-Only trial analysis suggested a significant dose-dependent effect of LPS on Test Day 1 with the 300 and the 200 μg/kg LPS groups exhibiting significantly reduced startle responses. On the second test day, the control animals displayed significant habituation to the tactile startle stimulus while the LPS animals did not. On the PPI trials, LPS animals exhibited normal prepulse inhibition. The acoustic PPI of the tactile startle response was significantly greater on Test Day 2 than on the first test day, regardless of treatment. These results suggest that “sickness behaviors” induced by high doses of LPS may include decreased non-voluntary motor activity, as measured by the tactile startle response. They also show that sensory processing, as measured by PPI, is not impaired with sickness.     

Effect of aripiprazole, risperidone, and olanzapine on the acoustic startle response in Japanese chronic schizophrenia

Background  

Studies have also shown that differences in the kind of the antipsychotics influenced disruption of the sensorimotor gating system, including prepulse inhibition (PPI), acoustic startle reflex (ASR), and habituation (HAB). We investigated the influence on startle response in chronic schizophrenia in 20 patients with schizophrenia taking risperidone, 21 patients with schizophrenia taking olanzapine, and 20 patients with schizophrenia taking aripiprazole.     

Reversal of scopolamine-induced disruption of prepulse inhibition by clozapine in mice

Prepulse inhibition (PPI) of the acoustic startle reflex refers to the reduction of the startle response to an intense acoustic pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus and provides a cross-species measure of sensory-motor gating. PPI is typically impaired in schizophrenia patients, and a similar impairment can be induced in rats by systemic scopolamine, a muscarinic cholinergic receptor antagonist that can evoke a range of cognitive and psychotic symptoms in healthy humans that are commonly referred to as the “anti-muscarinic syndrome” resembling some clinical features of schizophrenia. Scopolamine-induced PPI disruption has therefore been proposed as an anti-muscarinic animal model of schizophrenia, but parallel investigations in the mouse remain scant and the outcomes are mixed and often confounded by an elevation of startle reactivity. Here, we distinguished the PPI-disruptive and the confounding startle-enhancing effects of scopolamine (1 and 10 mg/kg, i.p.) in C57BL/6 wild-type mice by showing that the latter partly stemmed from a shift in spontaneous baseline reactivity. With appropriate correction for between-group differences in startle reactivity, we went on to confirm that the PPI-disruptive effect of scopolamine could be nullified by clozapine pre-treatment (1.5 mg/kg, i.p.) in a dose-dependent manner. This is the first demonstration that scopolamine-induced PPI disruption is sensitive to atypical antipsychotic drugs. In concert with previous data showing its sensitivity to haloperidol the present finding supports the predictive validity of the anti-muscarinic PPI disruption model for both typical and atypical antipsychotic drug action.     

Acoustic startle, prepulse inhibition, locomotion, and latent inhibition in the neuroleptic-responsive (NR) and neuroleptic-nonresponsive (NNR) lines of mice

The acoustic startle reflex (ASR) is inhibited by low intensity acoustic stimuli (prepulse inhibition; PPI) delivered prior to the startle stimulus. PPI may reflect underlying sensorimotor processes involved in the filtering of exteroceptive stimuli for their cognitive or physiological relevance. Latent inhibition (LI) is a cognitive process in which pre-exposure to the conditioned stimulus (CS) produces pro-active interference with the acquisition of an associative learning task. LI is thought to reflect a selective attention mechanism that contributes to an organism’s ability to adjust its behavior to changing contingencies of reinforcement. In the present series of experiments, the ASR, PPI at three prepulse intensities (56, 68, and 80 dB), locomotor activity, and LI using an active avoidance paradigm were assessed in mice bidirectionally selected from a heterogeneous stock for response (NR line) or non-response (NNR line) to neuroleptic-induced catalepsy. A randomly selected line was used as the control. Mice from the NNR line displayed weak startle responses and a complete absence of PPI. In contrast, the NR line displayed the largest ASR and the greatest PPI. The control line displayed ASRs and PPI values intermediate to the selected lines. Locomotor activity which is known to affect LI was lowest in the NR line but was similar in the NNR and control lines. In the LI paradigm, acquisition of the avoidance response was impaired in mice from the NR and control lines that were pre-exposed to the auditory CS (normal response). In contrast, the acquisition of the avoidance response in the NNR line was similar in CS pre-exposed and CS non-pre-exposed animals. Overall, the results demonstrate that some of the same genetic factors which regulate neuroleptic response also play a significant role in PPI and LI. Received: 17 April 1997/Final version: 28 January 1998     

Effects of alcohol on baseline startle and prepulse inhibition in young men at risk for alcoholism and/or anxiety disorders

OBJECTIVE: This study examined the hypothesis that a decreased reaction to alcohol and a deficit in prepulse inhibition (PPI) of the startle reflex are characteristics of male offspring of alcoholics without comorbid anxiety disorder. METHOD: Male offspring (N = 51) with a parental history of (1) alcoholism only, (2) anxiety disorder only, (3) alcoholism and anxiety disorder, and (4) no psychiatric disorder participated in an experiment examining the effects of alcohol on the acoustic startle reflex and on PPI. The experiment was carried out in two sessions in which subjects received an alcoholic beverage and placebo beverage on alternate days. RESULTS: The magnitude of startle was reduced by alcohol in each group. However, the degree of reduction was less in the offspring of alcoholics only compared to the other groups. In addition, PPI was reduced in the offspring of alcoholics only compared to the offspring of parents with no psychiatric disorder. CONCLUSIONS: A reduced reactivity to the effect of alcohol and a deficit in PPI might constitute vulnerability markers for alcoholism, but only in offspring of alcoholics without comorbid anxiety disorder.