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Effects of bromocriptine and haloperidol on prepulse inhibition: comparison of the acoustic startle eyeblink response and the N1/P2 auditory-evoked response in man.

Experiments with animals have shown that D2 dopamine receptors are involved in regulating prepulse inhibition (PPI) of the acoustic startle reflex (suppression of the reflex response evoked by a loud sound by prior presentation of a low-intensity stimulus). Recently we found that PPI of the human eyeblink startle response could be suppressed by a D2 receptor agonist, bromocriptine, and that this suppression could be reversed by a D2 receptor-blocking neuroleptic, haloperidol. The present work attempted to replicate this finding and to extend it to PPI of the N1/P2 component of the auditory-evoked potential. Eleven healthy males (18-30 years) participated in four sessions in which they received oral doses of placebo, bromocriptine 1.25 mg, haloperidol 3mg and combined treatment with bromocriptine 1.25 mg + haloperidol 3 mg, according to a balanced double-blind protocol. Thirty-minute simultaneous recordings of the electromyographic (EMG) responses of the orbicularis oculi muscle of the right eye and the vertex auditory-evoked potentials took place 120 min after ingestion of haloperidol and/or 90 min after ingestion of bromocriptine. Sound stimuli (1-kHz) were presented in 60 trials separated by variable intervals (mean 25 sec): (i) 40 msec 115 dB ('pulse alone': 20 trials); (ii) 40 msec 85 dB (20 trials); (iii) 40 msec 85 dB, followed after 120 msec by 40 msec 115 dB ('prepulse/ pulse': 20 trials). The amplitudes of the EMG and N1/P2 responses were not altered significantly by any of the treatments. Bromocriptine attenuated PPI of the EMG response significantly, this attenuation being absent following combined haloperidol/bromocriptine treatment. Neither bromocriptine nor haloperidol significantly altered PPI of the N1/P2 complex. Bromocriptine suppressed and haloperidol elevated serum prolactin levels, these changes being absent when the two drugs were given in combination. The results suggest that different mechanisms may be involved in regulating PPI of the eyeblink and the N1/P2 component of the auditory-evoked potential, and that D2 receptors may be involved in the former case, but not the latter.

Acoustic Stimulation↗

A crossover study of clocapramine and haloperidol in chronic schizophrenia.

Therapeutic efficacy and target symptoms with clocapramine were compared with those with haloperidol by the crossover method, in a total of 26 chronic schizophrenic patients, by administration of one of the drugs for the first 14 weeks and the other for the next 14 weeks. The final global improvement rating showed no significant difference between the two groups, but clocapramine administered as first drug appeared to have a more pronounced effect than haloperidol. According to the improvement rate in psychotic symptoms, clocapramine tended to be superior to haloperidol for motor retardation, scanty speech and disturbance of thought. In addition the frequency of side-effects was lower with clocapramine than with haloperidol. Neither the side-effects nor abnormal laboratory test results were severe enough to terminate the trial. Clocapramine is considered to be equivalent or superior to haloperidol in terms of anti-psychotic effect in chronic schizophrenia, and is relatively safer than haloperidol.

Adult↗

Possible toxic encephalopathy following high-dose intravenous haloperidol.

OBJECTIVE: To describe a case of possible toxic encephalopathy in a surgical patient receiving high-dose intravenous haloperidol. CASE SUMMARY: A 54-year-old African-American man was admitted for spinal fusion. His medical history included bipolar disorder and a cerebrovascular accident. His recovery from surgery was complicated by the development of agitation, which was treated with increasing doses of intravenous haloperidol. An electroencephalogram was consistent with toxic encephalopathy. The patient's mental status returned to normal 8 days after discontinuation of haloperidol. DISCUSSION: High-dose intravenous haloperidol for severe agitation has been reported as an effective and safe treatment option for the hospitalized patient. We report the occurrence of toxic encephalopathy in a patient who received high-dose intravenous haloperidol. CONCLUSIONS: Caution should be used when high-dose intravenous haloperidol is used in an agitated patient. If the patient's clinical response is paradoxical to what is anticipated and the resulting agitation is mistakenly attributed to inadequate treatment, increasingly higher doses may only aid in the development of toxic encephalopathy.

Antipsychotic Agents↗

Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.

A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.

Adult↗

Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial.

BACKGROUND: Despite several treatmentoptions, adherenceto therapy is poor in patients with bipolar disorder. AIMS: A double-blind, controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes. METHOD: Patients (n=347) were randomised to receive aripiprazole or haloperidol in this 12-week, multicentre study. The primary outcome measure was the number of patients in response (greater, similar 50% improvement from baseline in Young Mania Rating Scale score) and receiving therapy at week 12. RESULTS: At week 12, significantly more patients taking aripiprazole (49.7%) were in response and receiving therapy compared with those taking haloperidol (28.4%; P < 0.001). Continuation rates differed markedly between treatments (week 12: aripiprazole, 50.9%; haloperidol, 29.1%). Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (62.7% v. 24.0%). CONCLUSIONS: Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks.

Acute Disease↗

Determination of haloperidol in human serum by radioimmunoassay.

A radioimmunoassay has been developed which enables accurate determination of haloperidol in human serum. Antiserum was prepared by immunizing guinea pigs with haloperidol (O-carboxymethyl)oxime derivative (III) coupled with bovine serum albumin. With the antiserum, 3H-haloperidol and dextran-coated charcoal, the assay of haloperidol in serum was possible over a concentration range of 1 to 50 ng/ml, using 0.1 ml of human serum without the need of an extraction procedure. Data obtained by radioimmunoassay are in good agreement with those obtained by gas chromatography. No appreciable cross-reactivity was observed neither with haloperidol metabolites nor with other butyrophenone neuroleptics. Serum levels of haloperidol in schizophrenic patients receiving single oral dosing (6 mg/subject) have also been determined.

Antibodies↗

Effects of apomorphine on morphine analgesia during the state of dopaminergic supersensitivity after chronic treatment with haloperidol.

Morphine induced-reduction in response to a repetitive electrical stimulation of the tail was measured in acute rats and rats chronically treated with haloperidol (1 mg/kg/d, for 7 d) following pretreatment with apomorphine. In acute experiments, a significant enhancement of the anti-struggling action of morphine was produced by haloperidol (1 mg/kg, i.p.). Low doses of apomorphine (30-480 micrograms/kg, i.p.) had no influence on the suppressing action of morphine on the struggling response induced by the tail stimulation. Following chronic treatment with haloperidol, the inhibitory action of morphine on the tail stimulation-induced struggling response was dose-dependently inhibited by very low doses of apomorphine (60-480 micrograms/kg, i.p.). A significant increase in 3,4-dihydroxyphenylacetic acid (DOPAC) levels was observed after administration of haloperidol or morphine in acute rats, whereas no change in DOPAC levels was found after administration of morphine or apomorphine in chronically haloperidol-treated rats. In these animals, basal striatal DOPAC levels were significantly decreased compared with those of vehicle-treated animals controls. The present results suggest that in rats treated chronically with haloperidol, the suppressive action of a low dose of apomorphine on morphine analgesia is due to an increased sensitivity of postsynaptic dopaminergic receptors to apomorphine.

3,4-Dihydroxyphenylacetic Acid↗

Effect of cetrimide and ascorbic acid on in vitro human skin permeation of haloperidol.

Permeation of haloperidol through the human skin in vitro was studied with two enhancers, cetrimide and ascorbic acid, at various concentrations. Amber glass Franz-type diffusion cells were used for the permeation studies and haloperidol was made soluble in aqueous solution with the aid of lactic acid. Donor solutions were prepared by adding excess of haloperidol to 0.03% (v/v) lactic acid solution with or without enhancers at concentrations 0.1, 0.3 and 0.6% (w/v) and stirred for 36 h at 32 degrees C before filtering. Ascorbic acid gradually increased the solubility of the haloperidol from that of the control where as cetrimide did not show any effect. Cetrimide concentration dependent increase in the permeability coefficient of haloperidol was observed. Mechanism of enhancement by cetrimide was probed with the diffusion profile kinetics and Fourier transform infrared (FT-IR) spectroscopy. Cetrimide was found to increase the thermodynamic activity of the drug in the skin. IR spectra of the stratum corneum treated with cetrimide showed time-dependent decrease in the intensity of the spectrum and dose-dependent decrease of lipid band but no change in the protein conformation. Cetrimide appears to interact with both the dermal keratin and lipids and this interaction was found to be irreversible. Ascorbic acid although increased the flux of haloperidol to the same extent at all concentrations from that of the control, decreased the permeability coefficient and enhancer index in a concentration dependent manner and this is due to the increased solubility of the drug in the vehicle. Both the enhancers did not change the lag time from that of the control.

Antioxidants↗

Ginkgo biloba leaf extract (EGb 761) enhances catalepsy induced by haloperidol and L-nitroarginine in mice.

Ginkgo biloba extract EGb 761 has been reported to have therapeutic effects which have been attributed to anti-oxidant and free radical-scavenging activities, including a direct action on nitric oxide production. L G-nitro-arginine (L-NOARG), a nitric oxide synthase inhibitor, and haloperidol, a drug that blocks dopamine receptors, are both known to induce catalepsy in rodents. Nitric oxide has been shown to influence dopaminergic transmission in the striatum. The purpose of the present study was to evaluate the effect of the extract obtained from leaves of Ginkgo biloba tree EGb 761 on catalepsy induced by haloperidol or by L-NOARG. Albino Swiss mice (35-45 g, N = 8-12) received by gavage a single or repeated oral dose (twice a day for 4 days) of EGb 761 followed by ip injection of haloperidol or L-NOARG. After the treatments, the animals were submitted to behavioral evaluation using the catalepsy test. Acute treatment with 80 mg/kg EGb did not modify the catalepsy induced by L-NOARG but, the dose of 40 mg/kg significantly enhanced haloperidol-induced catalepsy measured at the 10th min of the test. After repeated treatment with 80 mg/kg EGb 761, a significant increase in the cataleptic effect produced by both haloperidol and L-NOARG was observed. These data show that repeated EGb 761 administration increases the effects of drugs that modify motor behavior in mice. Since the catalepsy test has predictive value regarding extrapyramidal effects, the possibility of pharmacological interactions between haloperidol and Ginkgo biloba extracts should be further investigated in clinical studies.

Animals↗

Relapse in patients with schizophrenia: a comparison between risperidone and haloperidol.

OBJECTIVES: To compare rates of rehospitalization and time to relapse in risperidone vs. haloperidol-treated schizophrenic patients discharged from the hospital. METHODS: Randomized controlled trial comparing risperidone and haloperidol regarding relapse in patients with schizophrenia treated with flexible doses during one year. RESULTS: Twenty patients were assigned to risperidone and 13 to haloperidol. One patient from each group withdrew consent and one patient in the risperidone group was lost for follow-up. Six (30.0%) patients in the risperidone group and 3 (23.1%) in the haloperidol group relapsed (p=1.00). However, time to relapse was shorter in the later (logrank =4.2; p=.04). When rehospitalized, patients in the risperidone group stayed 34.5 days (median) at hospital as compared to the haloperidol group (median of 61 days) (p=.61). CONCLUSION: The proportion of schizophrenic patients who relapsed was similar in both groups; However, time to relapse was shorter in the haloperidol-treated patients.

Adolescent↗

Use of antisera in the isolation of human specific conjugates of haloperidol.

1. Three conjugated metabolites of haloperidol were isolated from urine of patients on haloperidol and purified by h.p.l.c. with immunological detection, using three types of anti-haloperidol antisera. 2. Structures of the metabolites were: a sulphate conjugate of the 2-hydroxylated 4-fluorophenyl ring of reduced haloperidol (MH-1), a glucuronide conjugate at the same position as MH-1 (MH-2), and a glucuronide conjugate of the hydroxy group of haloperidol (MH-3). 3. MH-3 was the main urinary metabolite in volunteers receiving haloperidol, who excreted 18% of the dose in the 24 h urine as MH-3, while other conjugates were less than 1%. MH-3 could not be hydrolysed with beta-glucuronidase, due to steric hindrance. 4. Immunological detection of conjugated metabolites is very useful in metabolic studies in humans because of its sensitivity and specificity.

Adult↗

A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.

BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia. METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty-six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12. RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05). CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects.

Antipsychotic Agents↗

Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder.

BACKGROUND: Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile. The present study investigated the efficacy, safety, and tolerability of aripiprazole and haloperidol compared with placebo. METHOD: A 4-week, double-blind, randomized study, conducted at 36 U.S. centers between July 1997 and June 1998, compared aripiprazole (15 mg/day, 30 mg/day) to placebo, with haloperidol (10 mg/day) as an active control. Fixed doses of each agent were administered from day 1 throughout the study. A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative, PANSS-derived Brief Psychiatric Rating Scale (BPRS) core, Clinical Global Impressions (CGI)-Severity of Illness, and mean CGI-Improvement scores. Safety and tolerability evaluations included extrapyramidal symptoms (EPS), weight gain, serum prolactin level, and QTc interval. RESULTS: Both doses of aripiprazole and haloperidol, 10 mg, produced statistically significant (p < or = .05) improvements from baseline in PANSS total, PANSS positive, PANSS-derived BPRS core, and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint, compared with placebo. Aripiprazole, 15 mg, and haloperidol, 10 mg, significantly improved PANSS negative score compared with placebo. Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2. Unlike haloperidol, aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo. There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo, and no patients receiving aripiprazole experienced clinically significant increases in QTc interval. CONCLUSION: Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.

Acute Disease↗

A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis.

OBJECTIVE: Randomized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis. However, these results may not be generalizable to routine clinical practice. We evaluated the effectiveness, tolerability, and safety of olanza-pine, risperidone, and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical settings. METHOD: 172 patients participated in a practical clinical trial and were randomly assigned to haloperidol (N = 56), risperidone (N = 61), and olanzapine (N = 55). The mean modal daily doses were 5.4 mg/day for halo-peridol, 4 mg/day for risperidone, and 15.3 mg/day for olanzapine; 98.3% of subjects were drug naive at baseline. Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal (February 2001 to February 2005) intervention program of first-episode psychosis (schizophrenia spectrum disorders, DSM-IV criteria) are reported. RESULTS: All 3 treatments showed similar effectiveness in reducing the severity of general, negative, and positive symptomatology after 6 weeks of treatment, as reported by mean change in total Clinical Global Impressions-Severity of Illness scale, Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks. The proportion of study subjects responding, defined as 40% or greater BPRS total score improvement from baseline, was 57.1% (N = 32 of 56) haloperidol, 52.5% (N = 32 of 61) risperidone, and 63.6% (N = 35 of 55) olanzapine, with no statistical differences among groups. The frequency of extrapyramidal symptoms (chi(2) = 24.519; p < .001) and concomitant anticholinergic medication use (chi(2) = 57.842; p < .0001) was greater with haloperidol than olanzapine or risperidone. Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups (p < .001). CONCLUSION: Relatively low doses of haloperidol, risperidone, and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice.

Acute Disease↗

["More is less": a retrospective study of haloperidol dosages in acute schizophrenia].

UNLABELLED: With the background of a number of meta-analyses on the optimal neuroleptic dosages [1,2] the average daily dosage for the treatment of acute schizophrenic episodes recommended in the internal treatment guidelines of our psychiatric clinic was reduced from 24 mg to 15 mg haloperidol equivalent. In the present retrospective study it was investigated what effect this change in guideline had on the actual dosing behavior and on the efficacy and the side effect rate of the antipsychotic treatment. For this purpose all haloperidol treated patients of a two year interval prior to the change of the guideline (1987/88, n = 103) were compared with all treated of a two year interval (1991/92, n = 87) following it. RESULTS: The evaluation of the treatment data showed that the dosing guideline was adhered to and in 1991/92 on the average actually only 15 mg haloperidol were prescribed daily in acute schizophrenic episodes. The antipsychotic efficacy was just as good under this dosage as under the average daily dose of 24 mg haloperidol given in the preceeding interval; the average time in hospital was even reduced from 76 to 67 days. Under the lower daily doses an additional medication with biperiden was less often required. CONCLUSION: Average daily doses of 15 mg haloperidol appear to be at least equally as effective and more tolerable for the treatment of acute schizophrenic episodes than average daily doses of 24 mg haloperidol.

Acute Disease↗

Effect of haloperidol treatment on immunoreactive neuropeptide Y secretion into lateral cerebral ventricle of rats.

The study aimed to evaluate the effect of acute and 14-day haloperidol treatment (2 mg/kg ip) on release of neuropeptide Y-like immunoreactivity (NPY-LI) in non-anesthetized, freely moving rats by means of push-pull perfusion of the lateral cerebral ventricle. Twenty four hours after a single haloperidol injection NPY-LI release decreased by 15% (p < 0.05). No alterations were detected after 14-day haloperidol treatment. The study has confirmed that haloperidol alters the activity of neuropeptide Y system in the rat brain and suggested that acute haloperidol treatment inhibits the activity of the neuropeptide Y system at least in some brain structures surrounding the cerebral ventricles. The presented results have been discussed in view of our previous findings describing the haloperidol-induced changes in NPY-LI and NPY mRNA levels in the rat brain.

Animals↗

Superior efficacy of olanzapine over haloperidol: analysis of patients with schizophrenia from a multicenter international trial.

BACKGROUND: Previously, a double-blind, 6-week, parallel-group trial compared the therapeutic profiles of olanzapine (5-20 mg/day; N = 1,336) and haloperidol (5-20 mg/day; N = 660) in 1996 patients with DSM-III-R schizophrenia (83.1%) or schizophreniform (1.9%) or schizoaffective disorders (15.0%) and showed olanzapine to have a superior, broader spectrum of efficacy as well as a more favorable adverse event profile. The present post hoc analysis examined the efficacy of olanzapine compared with haloperidol in the schizophrenic cohort of that study and in subgroups of schizophrenic patients defined by baseline symptom profile and course of illness. METHOD: A total of 1,658 patients were included. Patients were included in analyses of change if they had both a baseline and at least 1 postbaseline measurement (N = 1,622; 1,096 olanzapine-treated patients, 526 haloperidol-treated patients). An analysis of variance was used to compare treatment effects on efficacy measurements including the Brief Psychiatric Rating Scale (BPRS; scored 0-6) and the Positive and Negative Syndrome Scale (total, positive subscale, and negative subscale scores). RESULTS: Olanzapine-treated patients exhibited statistically significantly greater improvements from baseline (last observation carried forward) on all efficacy measurements. Olanzapine-treated patients with predominantly positive, predominantly negative, or mixed symptoms had statistically significantly greater improvements in BPRS total scores compared with similar haloperidol-treated patients. Patients with primarily chronic negative symptoms and patients with chronic or subchronic courses of illness had statistically significantly greater mean improvements from baseline on the BPRS total with olanzapine compared with haloperidol. Furthermore, within the olanzapine treatment group, patients with a subchronic course of illness had greater mean improvements than patients with a chronic course of illness. CONCLUSION: Olanzapine was more effective than haloperidol in treating a varied spectrum of patients with schizophrenia, including patients with positive, negative, or mixed symptom profiles and either a chronic or subchronic course of illness.

Adult↗

Haloperidol reduces stimulant and reinforcing effects of ethanol in social drinkers.

BACKGROUND: Despite abundant preclinical support for a role of dopamine (DA) in the stimulant-like and reinforcing effects of ethanol, there have been few studies directly investigating this mechanism in human subjects. This study examined the effect of a DA antagonist, haloperidol, on the subjective stimulant-like effects of acute doses of ethanol and on ethanol reinforcement in healthy human volunteers. It was hypothesized that a low dose of the DA D2/D3 antagonist haloperidol (3 mg) would attenuate stimulant-like subjective effects of ethanol (0.75 g/kg) and reduce the number of drinks chosen during a subsequent choice phase. METHODS: Seventeen healthy men and women, 21 to 35 years old, participated in four laboratory sessions conducted at 1-week intervals. During the four sessions they received, in randomized order under double-blind conditions, capsules containing haloperidol or placebo followed by three drinks containing ethanol (0.75 g/kg) or placebo, at 30-min intervals. Subjective and behavioral responses were measured before and after the beverages. After the third beverage, subjects could choose up to five additional doses of the beverage they had ingested. RESULTS: Haloperidol reduced the number of ethanol beverages subjects chose without altering placebo beverage choices. Haloperidol also dampened some of the subjective effects of ethanol, especially in subjects who experienced stimulation after ethanol. Haloperidol reduced stimulant-like and euphorigenic effects of ethanol in subjects who experienced stimulant effects (n = 8) but had no effect in subjects who did not experience stimulation from ethanol (n = 9). CONCLUSIONS: These findings suggest that DA plays a role in the stimulant-like, euphorigenic, and reinforcing qualities of ethanol in humans. However, the findings also raised new questions about the link between the subjective and reinforcing effects of ethanol.

Adult↗