摘要:

Schizophrenic patients exhibit deficits in indices of sensorimotor gating, such as habituation and prepulse inhibition (PPI) of the startle reflex. Hallucinogenic drug-induced states are putative models for the early and acute stages of schizophrenic and schizophrenia-spectrum disorders. Hallucinogenic drugs have been shown to disrupt PPI and/or retard habituation of the startle reflex in animal models of schizophrenia, consistent with the view of hallucinogen-induced states as 'model psychoses'. We evaluated the effects of the hallucinogen psilocybin on PPI and habituation of the startle reflex in a doubleblind, placebo-controlled human study with 12 healthy subjects. In contrast to animal studies, in our small human sample, psilocybin increased PPI, while having no clear effect on habituation (n=6). These findings must be considered preliminary because several factors, including dose regimens and experimental parameters, may influence the results of studies on startle plasticity. Further investigations both with psychotic patients in different stages of the disease and with human and animal models of schizophrenia are needed in order to explore the effects of hallucinogens on sensorimotor gating and the relationship between information processing in hallucinogenic drug-induced states and the naturally occurring psychoses.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effects of acute administration of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers on habituation and prepulse inhibition (PPI) of the acoustic startle reflex in two experiments. In Experiment 1, 40 male non–smoker volunteers were tested for habituation and PPI (defined as percentage reduction of the pulse-alone amplitude; prepulses 9 dB above background) before and after double–blind administration of either 2mg haloperidol or placebo. No influence of haloperidol was observed on either habituation or PPI of the startle reflex in this experiment. In Experiment 2, 60 male volunteers underwent startle testing before and after double-blind administration of a single oral dose of 5 mg haloperidol, 5 mg damphetamine or placebo. Habituation and PPI (prepulses 15 dB above background) for the placebo group did not differ significantly from that observed for the rf-amphetamine or for the haloperidol group. However, in a subgroup of smoking subjects, both d-amphetamine and haloperidol reduced PPI as compared to that observed prior to drug administration. The implications of these findings in relation to animal pharmacological studies and observed sensorimotor gating deficits in schizophrenia are discussed. Behav Pharmacol 1998; 9:567— 576 © 1998 Lippincott Williams & Wilkins.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Attenuation of hypothalamo-pituitary-adrenal (HPA) function in laboratory rodents has been found to reduce the reinforcing effects of cocaine. To examine whether attenuation of HPA function reduces the effects of cocaine in humans, one female and seven male 'crack' cocaine abusers were pretreated with three doses of ketoconazole (0, 600, 1200 mg), an inhibitor of adrenocorticoid biosynthesis, 1 h before receiving cocaine. Three doses of smoked cocaine (0, 12, 50 mg) were administered in counterbalanced order under each ketoconazole condition. Ketoconazole dose-dependently reduced cocaine-induced cortisol, but not adrenocorticotropin (ACTH) release, and attenuated the cocaine-induced increase in heart rate and blood pressure. Plasma ACTH levels were more predictive of blood pressure changes than either cocaine or cortisol levels. Suppression of cortisol secretion was not associated with a reduction in ratings of the subjective effects of cocaine. These results support a role for the HPA axis in the cardiovascular effects of cocaine, but do not support a role for the HPA axis in the subjective effects of cocaine. To the extent that self-administration can be predicted by subjective effects, these results further argue that the HPA axis does not play a critical role in cocaine self-administration by humans.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Eight male frequent cocaine smokers participated in a 44- to 47-day inpatient and outpatient study to assess the effects of the noncompetitive iV-methyl-D-aspartate (NMDA) antagonist, memantine, on cocaine self-administration, subjective effects, and psychomotor performance. Participants were maintained on memantine (0 and 20 mg daily) for 7-10 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition, participants smoked four doses of cocaine base (0,12, 25 and 50 mg), and were subsequently given five opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher ($5.00). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose was systematically varied. Vital signs were recorded every 2 min, and subjective effects were assessed at baseline and after each cocaine or voucher delivery. In addition, psychomotor performance was assessed before and after each self-administration session. Memantine maintenance was not associated with changes in psychomotor performance or the number of cocaine doses chosen each session. Memantine maintenance was, however, associated with significant increases in some subjective effects of cocaine, including ratings of 'good drug effect', 'high', 'potency', 'quality', and street value. These data suggest that NMDA antagonists may have limited usefulness as treatment medications for cocaine abuse

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Delta-9-tetrahydrocannabinol (THC) is frequently found in the blood of drivers involved in automobile accidents, and marijuana use has been associated with impaired field sobriety test performance. The present study used a within-subject design to compare the effects of marijuana (0, 1.77, or 3.95% THC) on equilibrium and simulated driving. Ten marijuana users (seven men, three women) smoked one marijuana cigarette at the beginning of each session. Then 2 min later, they began a 60-min test battery that included subjective effects scales, a computerized test of body sway, a rapid judgment task and brake latency measurement in a driving simulator, critical flicker fusion (CFF), and a choice reaction time task (CRT). Self-report ratings of 'high' and 'drug potency' increased comparably following both active doses. The high, but not the low, dose significantly increased body sway. The high dose also marginally increased brake latency by a mean of 55 ms (P<0.10), which is comparable to an increase in stopping distance of nearly 5 feet at 60mph Judgment, CFF, and CRT scores did not differ across dose conditions. The equilibrium and brake latency data with 3.95% THC are similar to prior results in our laboratory in participants with breath alcohol concentrations near 0.05%.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Moderate caffeine consumers (n=64, mean caffeine intake 453 mg/day) were deprived of caffeine overnight and semirandomly allocated to four treatment groups, designated PPP, CPP, CCP and CCC, where P is placebo and C is caffeine (1.2 mg/kg, giving an amount of caffeine similar to that consumed in a serving of ground coffee). Caffeine or placebo (i.e. no caffeine) were administered double-blind in novel fruit juice drinks at 10:15, 11:30 and 13:00 h on the test day. Before (baseline), and 45min after each of these times the participants completed a mood questionnaire and begun psychomotor performance tests lasting 25min (1-min tapping task, and a long-duration simple reaction time task (SRT)). Caffeine significantly increased energetic mood and improved psychomotor performance relative to placebo. Caffeine had particularly marked effects on SRT performance, ameliorating the slowing of performance with time on task and removing the post-lunch dip in performance. However, the three caffeine treatments, CPP, CCP and CCC, were equally effective. That is, mood and performance were improved to the same extent by one, two and three spaced doses (totalling 86,172 and 258 mg) of caffeine. This result is consistent with previous findings indicating a flat dose-response relationship for the psychoactive effects of caffeine; and because of the adverse effects (e.g. fatigue) associated with overnight caffeine deprivation, it suggests that there is little net benefit to be gained from frequent caffeine use. At the very least, it appears that the psychostimulant effects of caffeine cannot on their own account for the typical pattern of consumption of caffeinecontaining drinks. Behav Pharmacol 1998; 9:611-618 © 1998 Lippincott Williams & Wilkins

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Ethanol is an effective reinforcer but, in common with other drugs of abuse, it may derive some of its reinforcing properties from the effects it has on behaviour maintained by other reinforcers. However, any assessment of ethanol's hypothesized effect on behaviour maintained by other reinforcers must take into account the fact that ethanol may have multiple mechanisms of action. In order to address this problem the experiments reported herein used a procedure based upon Herrnstein's Matching Law which allowed joint assessment of subjects' motor capacity and reinforcer sensitivity. The effect of ethanol (0, 0.3, and 0.6 g/kg) on motor capacity and reinforcer sensitivity was assessed by studying behaviour maintained by monetary reinforcement. In the first experiment the procedure was validated by showing that the behaviour of subjects was sensitive to changes in reinforcer value and in the second experiment 0.6 g/kg ethanol reduced motor capacity but did not affect reinforcer sensitivity. As a secondary hypothesis we also studied the effect of mood on reinforcer sensitivity and motor capacity. It was found that lower mood scores (lower hedonic tone) were associated with reduced reinforcer sensitivity and that male subjects showed higher motor capacity than females. However, there was also a mood by sex interaction, which indicated that higher motor capacity in males was only found in the presence of lower mood scores. The results are discussed in relation to the mechanisms of ethanol's dopaminergic effects, interactions between ethanol and other drugs of abuse, and the changes in reinforcer sensitivity which are thought to occur in depression.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effects of exposure to an alcohol-related cue (drinking low-alcohol beer) and a musical depression/elation mood induction procedure, on craving, motivation and liking for alcohol, were studied in male and female recreational drinkers. Alcohol craving was assessed using the multidimensional desires for alcohol questionnaire (DAQ), motivation for alcohol was assessed by performance on a progressive ratio (PR) task reinforced with small volumes (25 ml) of low-alcohol beer, and liking for the reinforcers earned in the PR task was assessed using a visual analogue scale. Consumption of a half-pint of low-alcohol beer increased alcohol craving in male subjects but had no effect or decreased craving in female subjects. Subsequent induction of a depressed mood increased craving scores, relative to elated or neutral mood groups, but these effects were confined to abstinent (non-cued) subjects, both male and female. Performance on the PR task correlated significantly with one of the four factors of the DAQ, negative reinforcement, and was increased by induction of a depressed mood in abstinent female and cued male subjects. Reinforcer liking was unchanged following mood induction in male subjects, but decreased in both groups of female subjects. To summarize, the cue of drinking low-alcohol beer increased alcohol craving in men but not in women, and induction of a depressed mood increased alcohol craving and motivation, but also decreased alcohol liking. These effects were present to different extents in different cue/gender subgroups, and were partially independent. Behav Pharmacol 1998; 9:631-642 © 1998 Lippincott Williams & Wilkins

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Eighteen male social drinkers underwent four training sessions during which they ingested two colour-coded drinks (red or blue, balanced for drink type); one containing alcohol (aliquots of 0.1 g/kg) and the other placebo (aliquots of orangeade). Following the training sessions, subjects were presented with both drinks, and instructed to choose the drink they felt like consuming and to indicate their preference for their chosen drink over the other drink. In addition, they were instructed to consume the first drink but that all subsequent drinks (total of six drinks), offered at 10-min intervals, were optional. A number of trait characteristics were assessed including alcohol outcome expectancies, drinking habits and personality traits. The acute effects of alcohol on mood was also evaluated by comparing subjective ratings following alcohol and placebo during the training sessions. Of the 18 subjects, 12 chose alcohol at least once ('samplers'), whereas six never chose alcohol ('non-samplers'). Over the three sessions, however, alcohol and placebo were chosen equally. When alcohol was chosen, subjects drank significantly more than when placebo was chosen, which may be consistent with a priming effect of drinking alcohol. The amount of alcohol drunk was seen to correlate with the alcohol expectancy factor 'sociability'. Subjective reports of feeling 'alert', 'clear-headed', 'quick-witted', and 'attentive' all showed a main effect of choosing behaviour (i.e 'samplers'/'non-samplers'). Further analysis indicated that this effect was due to 'samplers' reporting increased subjective ratings of these mood states following the ingestion of alcohol compared to 'non-samplers'. These increased subjective ratings were also positively correlated with the amount of alcohol consumed by the subjects during the choice procedure. No other relationships were found between the amount of alcohol consumed and any of the other state or trait measures. These data suggest that social drinkers who sample alcohol in a laboratory setting can be primed by alcohol to consume more. The results also indicated that the amount drunk was related to the degree to which subjects expected alcohol to increase sociability and to reports of subjective stimulant effects of alcohol (e.g. 'alert', 'clear-headed', 'quickwitted', and 'attentive'). Behav Pharmacol 1998; 9:643-653 © 1998 Lippincott Williams & Wilkins

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID