d-Amphetamine raises serum prolactin in man: evaluations after chronic placebo, lithium and pimozide treatment.

One of the major biochemical effects of d-amphetamine is the release and uptake inhibition of dopamine (DA). We measured the effect of d-amphetamine upon prolactin release which is inhibited by DA and stimulated by serotonin. d-Amphetamine (20 mg i.v.) significantly raised the serum prolactin levels of drug-free schizophrenic patients over preinfusion levels and levels following a paired placebo lactose infusion. Amphetamine infusions were repeated after both chronic DA blockade with pimozide and after chronic lithium treatment that has been reported to attenuate amphetamine effects. These chronic pretreatments did not prevent significant increases in prolactin following d-amphetamine infusions. Pimozide raised preinfusion prolactin levels but lithium had no effect. Further studies are needed to clarify the d-amphetamine-induced rise in prolactin.     

On the hyperthermic response to d-amphetamine in the decapitated rat

Injection of d-amphetamine (10 mg/kg i.p.) in the decapitated rat causes an increase in body temperature, oxygen consumption and heart rate and a decrease in skin temperature. These effects could be reduced or blocked by administration of α- and β-blocking agents. In the decapitated rats in which the content of endogenous catecholamine was reduced by 6-hydroxydopamine treatment and/or adrenalectomy the effects of d-amphetamine were also reduced. Thus it can be concluded that d-amphetamine has a peripheral calorigenic effect due to release of catecholamines. This calorigenic effect of d-amphetamine is resistent to treatment with pimozide in contrast to the pimozide sensitive, central thermogenic effect described by other authors.     

Sleep in chronic chorea patients after therapy with sodium valproate

In previous researches spontaneous nocturnal sleep in chronic chorea showed short total sleep time, prolonged sleep latency, several awakenings, reduction of REM sleep time, decrease in slow waves sleep, strong increase in sleep spindles. Some of these alterations improved after therapy with lithium, haloperidol and lithium, pimozide. Since the concentration of GABA has been found to be reduced in patients with Huntington's chorea, we studied the effect of sodium valproate, a drug that enhances GABA inhibition in cerebral cortex, on nocturnal sleep of six patients with chronic chorea, aged 35 to 60 years (mean 47,3). Nocturnal polygraphic records (EEG, EOG, EMG of chin muscles) were carried out after two consecutive adjustative nights, both before therapy and after sixty days of treatment with sodium valproate (800-2000 mg four times a day, orally). Moreover, chorea, finger dexterity and gait were each rated once a week by three members of the research team and by one independent observer, using a five points rating scale from 0 (normal) to 4 (very severely abnormal). Before therapy the sleep parameters were in accordance with our previous results in chronic choreic patients. After two months therapy we observed a statistically significant (P less than 0.05) reduction of awakenings and of wake time. Sodium valproate produced no objective change in any of the parameters of motor function studied. If singularly examined, however, a reduction of chorea was obtained only in a patient, whose favourable response to therapy was also demonstrated by the normalization of other sleep parameters. These data stress the importance of sleep study in extrapyramidal disorders and suggest a different involvement of GABA-mediated transmission in various patients with chronic chorea.     

Biphasic effects of pimozide on sleep-wakefulness in dogs

Sleep-wakefulness patterns in dogs were studied using computerized on-line power spectral analysis and off-line automatic stage-classification during control recordings and after oral treatment with three doses of the specific dopamine blocker pimozide. A biphasic effect on sleep-wakefulness patterns was found. At 0.016 mg/kg (the ED₅₀-value for the antagonism of apomorphine-induced vomiting in dogs), pimozide significantly increased the time spent awake, and significantly decreased slow wave sleep and REM sleep. No significant effects were obtained with a four times higher dose of pimozide. At 0.16 mg/kg, pimozide significantly decreased the time spent awake and significantly increased slow wave sleep and REM sleep. The effects appear the opposite of those described for apomorphine and suggest that dopamine plays a role in the physiology of sleep-wakefulness regulation.     

Implementation of 12-hour shifts in a Brazilian petrochemical plant: impact on sleep and alertness

A recent worldwide trend in chemical and petrochemical industries is to extend the duration of shifts. Optimization of the labor force to reduce costs is one reason to increase the length of working time in a shift. Implementation of 12h shifts is a controversial decision for managers and scientists. Literature reviews show alertness is lower during the nighttime hours, and sleep duration is reduced and worse during the daytime. The main objective of this study was to evaluate the impacts of 12h shifts on alertness and sleep. To evaluate the duration and quality of sleep and alertness during work, 22 male shift workers on a continuous rotating schedule at a petrochemical plant completed activity logs and estimated alertness using analog 10-cm scales for 30 consecutive days, three times (at 2h, 6h, and 10h of the shift) every work shift. Statistical tests (analysis of variance [ANOVA] and Tukey) were performed to detect differences between workdays and off days. The shift schedule was 2 days/3 nights/4 off days, followed by 3 days/2 nights/5 off days, followed by 2 days/2 nights/5 off days. Sleep duration varied significantly (p < .001) among the work shifts and off days. Comparing work nights, the shortest mean sleep occurred after the second night (mean = 311.4 minutes, SD = 101.7 minutes), followed by the third night (mean = 335.3 minutes, SD = 151.2 minutes). All but one shift (sleep after the first work night) were significantly different from sleep after the first 2 workdays (p < .002). Tukey tests showed no significant differences in sleep quality between workdays and nights, with the exception of sleep after the third day compared to sleep after night shifts. However, significant differences were detected between off days and work nights (p < .01). ANOVA analysis showed borderline differences among perceived alertness during day shifts (p = .073) and significant differences among the hours of the shifts (p = .0005), especially when comparing the 2nd hour of the first day with the 10th hour of all the day shifts. There were no significant differences in perceived alertness during night work among the first, second, and third nights (p = .573), but there were significant differences comparing the times (2nd, 6th, 10th hour) of the night shifts (p < .001). The evaluation of sleep (duration and quality) and level of alertness have been extensively used in the literature as indicators of possible performance decrements at work. The results of this study show poorer sleep after and significantly decreased alertness during night work. Shifts of 12h are usually implemented for technical and economic reasons. These results point out the necessity of a careful trade-off between the financial and technical gains longer shifts might bring and the possible losses due to incidents or accidents from performance decrements during work.     

Potentiation by naltrexone of d-amphetamine-induced behavioral suppression and its reversal by clonidine

Rats were trained to perform a fixed ratio-15 operant for food reinforcement during a 30 minute daily session. Naltrexone, in doses up to 45 mg/kg administered 15 min before the behavioral session, failed to disrupt responding. However, 0.3 and 1.0 mg naltrexone/kg produced a dose related potentiation of the operant behavioral suppression induced by 1.0 mg d-amphetamine/kg injected immediately before the session. The naltrexone/d-amphetamine combination also produced excessive salivation and postural abnormalities not seen when either drug was administered alone. [A subsequent study indicated that the salivation induced by naltrexone in combination with d-amphetamine may require previous exposure to naltrexone and/or d-amphetamine.] Blockade of dopamine receptors with pimozide did not modify the interaction. Functional noradrenergic blockade with a low dose of clonidine significantly reversed the potentiated suppression, of operant behavior, as well as the excessive salivation and abnormal posture. These data suggest that there is an important noradrenergic component to the interaction of naltrexone with d-amphetamine. The impressive interaction of behaviorally inactive doses of naltrexone with a moderate dose of d-amphetamine reported here for rats may have clinical implications for detoxified opiate addicts maintained on naltrexone in antagonist therapy programs.     

Daytime noise and subsequent night sleep in man

The effects of daytime noise on recovery processes during subsequent undisturbed night sleep were studied in six healthy men (21-27 years), exposed to 80 dB (A) pink noise 8 h per day for 2 days. Sleep EEG, ECG, and respiration were recorded in the laboratory for five consecutive nights: two baseline nights, two nights following noise stimulation, and again one baseline night. Additionally questionnaire data were collected, reflecting a subjective impairment of the recovery function of sleep after noise exposure. EEG sleep data of the first post-noise night showed an increase in slow wave sleep with a simultaneous decrease in stage 2 sleep. During the second post-noise night these changes were less prominent. Three subjects additionally showed an instability in the sleep course coinciding with elevated heart and respiration rates. However, altogether the autonomic parameters were not clearly affected by the noise exposure. The findings support the assumption that strong daytime noise may interfere with subsequent sleep processes.     

IMPLEMENTATION OF 12-HOUR SHIFTS IN A BRAZILIAN PETROCHEMICAL PLANT: IMPACT ON SLEEP AND ALERTNESS

A recent worldwide trend in chemical and petrochemical industries is to extend the duration of shifts. Optimization of the labor force to reduce costs is one reason to increase the length of working time in a shift. Implementation of 12h shifts is a controversial decision for managers and scientists. Literature reviews show alertness is lower during the nighttime hours, and sleep duration is reduced and worse during the daytime. The main objective of this study was to evaluate the impacts of 12h shifts on alertness and sleep. To evaluate the duration and quality of sleep and alertness during work, 22 male shift workers on a continuous rotating schedule at a petrochemical plant completed activity logs and estimated alertness using analog 10-cm scales for 30 consecutive days, three times (at 2h, 6h, and 10h of the shift) every work shift. Statistical tests (analysis of variance [ANOVA] and Tukey) were performed to detect differences between workdays and off days. The shift schedule was 2 days/3 nights/4 off days, followed by 3 days/2 nights/5 off days, followed by 2 days/2 nights/5 off days. Sleep duration varied significantly (p <. 001) among the work shifts and off days. Comparing work nights, the shortest mean sleep occurred after the second night (mean = 311.4 minutes, SD = 101.7 minutes), followed by the third night (mean = 335.3 minutes, SD = 151.2 minutes). All but one shift (sleep after the first work night) were significantly different from sleep after the first 2 workdays (p <. 002). Tukey tests showed no significant differences in sleep quality between workdays and nights, with the exception of sleep after the third day compared to sleep after night shifts. However, significant differences were detected between off days and work nights (p <. 01). ANOVA analysis showed borderline differences among perceived alertness during day shifts (p =. 073) and significant differences among the hours of theshifts(p =. 0005), especially when comparing the 2nd hour of the first day with the 10th hour of all the day shifts. There were no significant differences in perceived alertness during night work among the first, second, and third nights (p =. 573), but there were significant differences comparing the times (2nd, 6th, 10th hour) of the night shifts (p ≤. 001). The evaluation of sleep (duration and quality) and level of alertness have been extensively used in the literature as indicators of possible performance decrements at work. The results of this study show poorer sleep after and significantly decreased alertness during night work. Shifts of 12h are usually implemented for technical and economic reasons. These results point out the necessity of a careful trade-off between the financial and technical gains longer shifts might bring and the possible losses due to incidents or accidents from performance decrements during work. (Chronobiology International, 17(4), 521–537, 2000)     

Differential effects of D- and L-amphetamine on the sleep of depressed patients.

Dextro (d-) and levo (1-) amphetamine produced different EEG sleep changes in depressed patients. Each patient received placebo or one of the isomers (30 mg base) at 7:25 a.m. in a double blind fashion. The patients were studied under two conditions: without treatment with lithium carbonate and with treatment with lithium carbonate (0.9–2.1 gm/day beginning a minimum of 10 days before study). Both isomers reduced REM sleep and the proportion of total sleep spent in REM (the REM%). No REM rebound was observed on the night following REM suppression. Only d-amphetamine delayed sleep onset and reduced Total sleep time, NREM sleep time, and Sleep Efficiency. The same changes were observed with and without lithium carbonate treatment.     

Fitness facilitates sleep

Eight army recruits were studied at the start, middle, and end of their initial 18-week training programme. At each point the subjects were studied for four consecutive nights in the sleep laboratory. Their sleep was characterized by the means of the recordings on the last two nights. Within 2 days of the sleep recordings (but never on the same day) each subject spent 2 non-consecutive days in the exercise laboratory. On the 1st day a maximum oxygen consumption (VO2 max) measurement was performed on a treadmill and on the 2nd day a 24-min progressive exercise bicycle ergometer test was carried out with simultaneous venous sampling (for lactic acid measurements) and oxygen consumption recordings from which the lactate turn point (LTP) was calculated. LTP was used as a measure of fitness. Approximately 1 week after the above measures lean muscle mass as calculated by total body potassium estimation was obtained for each subject. Slow wave sleep (SWS) as a percentage of total sleep time increased significantly between the start and the measurements at 9 and 18 weeks, being 21.9%, 29.9%, and 28.5% respectively. Anaerobic threshold increased significantly (P less than 0.05) over the first 9 weeks and continued to increase to the end of the training period (P less than 0.001) using VO2 when lactate level was 2 mmol/l as a percentage of VO2 max. With increase in fitness, sleep onset latency and wake time during sleep decreased and sleep efficiency improved. The results suggest that as fitness increases sleep quality improves.     

L-tyrosine cures, immediate and long term, dopamine-dependent depressions. Clinical and polygraphic studies

Twelve patients with polysommographic and clinical signs of dopamine-dependent depression (DDD) received, after a short-lasting trial with the dopamine agonist Piribedil, a treatment with oral-tyrosine (3,200 mg/day). On the very first day of treatment a return to mood, as judged by clinical impression and MADRS scores was observed. Sleep recordings performed on nights following days 1, 2, 7 and 8 of treatment showed an immediate improvement of those sleep parameters differentiating the more clearly DDD from other types of depression. More than 50 patients have now been treated successfully for periods ranging from a few months to almost 2 years. This treatment is ineffective in other types of depression.     

Ibogaine reduces amphetamine-induced locomotor stimulation in C57BL/6By mice, but stimulates locomotor activity in rats.

The effect of ibogaine hydrochloride on locomotor stimulation induced by d-amphetamine sulfate was tested in male C57BL/6By mice and in female Sprague-Dawley rats. In mice, locomotor stimulation induced by d-amphetamine at 1 or 5 mg/kg s.c. was reduced by prior administration of one or two injections of ibogaine (40 mg/kg), given 2 or 18 hours earlier. This reduction in locomotor activity persisted for two days. Locomotor stimulation induced by a higher dose (10 mg/kg) of d-amphetamine was not reduced by such prior administration of ibogaine. A lower dose of ibogaine (20 mg/kg) did not reduce the subsequent locomotor activity induced by d-amphetamine. Ibogaine decreased striatal dopamine levels, while d-amphetamine increased them. Ibogaine treatment (2 x 40 mg/kg, 18 hours apart) induced a decrease by 30% in the level of striatal dopamine and its metabolites measured in tissue extracts 3 hours after the second ibogaine injection. One hour after d-amphetamine (5 mg/kg) administration, the level of striatal dopamine increased by 26%. Although the level of striatal dopamine was initially lower in the ibogaine-pretreated mice, d-amphetamine (5 mg/kg) administration induced an increase in striatal dopamine and its metabolites. The effect of ibogaine seems to be species specific, since in rats pretreated with ibogaine 18 hours before d-amphetamine, locomotor stimulation induced by d-amphetamine was further increased. In addition, the in vitro electrical-evoked release of [3H]dopamine from striatal tissue was either unchanged or inhibited in the presence of d-amphetamine, and after ibogaine pretreatment in vivo, the release of tritium in the presence of d-amphetamine was inhibited or stimulated in mice and rats, respectively.     

Effects of dopaminergic and cholinergic interactions on rat behavior.

The present work studied the effects of dopaminergic and muscarinic receptor agonists and antagonists on rat locomotor activity and catalepsy. Results showed that carbachol at the highest dose used (10 mg/kg, p.o.) decreased and pimozide at the dose used abolished locomotor activity. Atropine at a low dose (1 mg/kg, p.o.) increased and at a high dose decreased this parameter. Mazindol at a high dose also increased locomotor activity. A significant and dose-dependent increase in the time on the bar was observed in animals treated with carbachol or pimozide as compared to controls. The increase observed with pimozide was greater than 60 s. Effects of carbachol on locomotor activity were observed already after the first drug exposure, but the increased time on bar produced by this drug in the test of catalepsy was observed only after repeated exposure (7th day). The effect of the highest dose (10 mg/kg, p.o.) of atropine (decreased activity) as related to the lowest one was evident at the 7th day, but the increased locomotor activity seen at the low dose was detected already at the first day. There was a predominance of the effect of pimozide on the open field as well as on catalepsy after its association with each one of the three doses of carbachol. The association of atropine and mazindol did not seem to alter locomotor activity and catalepsy as related to each drug alone. Our results indicate that interactions between dopaminergic and cholinergic systems play an important role on behavior and motor functions.     

Influence of repeated passive body heating on subsequent night sleep in humans

Experiments were carried out on four healthy male subjects in two separate sessions: (a) A baseline period of two consecutive nights, one spent at thermoneutrality [operative temperature (To) = 30 degrees C, dew-point temperature (Tdp) = 7 degrees C, air velocity (Va) = 0.2 m.s-1] and the other in hot condition (To = 35 degrees C, Tdp = 7 degrees C, Va = 0.2 m.s-1). During the day, the subjects lived in their normal housing and were engaged in their usual activities. (b) An acclimation period of seven consecutive daily heat exposures from 1400 to 1700 hours (To = 44 degrees C, Tdp = 29 degrees C, Va = 0.3 m.s-1). During each night, the subjects slept in thermoneutral or in hot conditions. The sleep measurements were: EEG from two sites, EOG from both eyes, EMG and EKG. Esophageal and ten skin temperatures were recorded continuously during the night. In the nocturnal hot conditions, a sweat collection capsule recorded the sweat gland activity in the different sleep stages. Results showed that passive body heating had no significant effect on the sleep structure of subsequent nights at thermoneutrality. In contrast, during nights at To = 35 degrees C an effect of daily heat exposure was observed on sleep. During the 2nd night of the heat acclimation period, sleep was more restless and less efficient than during the baseline night. The rapid eye movement sleep duration was reduced, while the rate of transient activation phases observed in sleep stage 2 increased significantly. On the 7th night, stage 4 sleep increased (+68%) over values observed during the baseline night.(ABSTRACT TRUNCATED AT 250 WORDS)     

Propofol-Induced Sleep: Efficacy and Safety in Patients with Refractory Chronic Primary Insomnia

Insomnia, defined as difficulty in falling asleep and/or staying asleep, short sleep duration, or poor quality sleep, is a common sleep disorder affecting 30-40% of adult population. We have conducted a randomized, double-blind, placebo-controlled study to test if anesthesia is therapeutically beneficial in patients with refractory chronic primary insomnia. We have assessed the efficacy and safety of propofol-induced sleep in these patients. This study comprised of 103 patients with refractory chronic primary insomnia (including 59 non-pregnant, non-lactating women; 28-60 years) and the participants were randomized to receive either physiological saline (placebo) (n = 39) or 3.0 g/l propofol (n = 64) in a 2-h continuous intravenous infusion for five consecutive nights. The Leeds Sleep Evaluation Questionnaire was used for the subjective assessment of sleep, and polysomnography was used for the objective measurement of sleep architecture and patterns. The assessments were done prior to and at the end of the 5-day treatment and 6 months after treatment period. The adverse effects of the treatment were also recorded. A 2-h continuous intravenous infusion of 3.0 g/l propofol for five consecutive nights improved the subjective and objective assessments of sleep in 64 patients with refractory chronic primary insomnia. This improvement occurred immediately after the therapy and persisted for 6 months. No serious adverse events were noticed during the period of drug administration or 6 months after the treatment. Propofol therapy is an efficacious and safe choice for restoring normal sleep in patients with refractory chronic primary insomnia.     

Tolerance to d-amphetamine: behavioral specificity.

In a Y-maze exploratory task mice tend to enter that compartment which was least recently visited (spontaneous alternation). Low doses of d-amphetamine (1.0 mg/kg) reduce alternation to chance levels, while high doses (10.0 mg/kg) result in animals successively visiting only two compartments of the Y-maze (perseveration). Following daily d-amphetamine injection (1.0 or 10.0 mg/kg) over a 30 day period tolerance to the d-amphetamine induced perseveration was observed; however, chronic amphetamine treatment did not modify the locomotor stimulating effects of d-amphetamine or the reduction of alternation to chance levels produced by low doses of the drug. It was hypothesized that tolerance to d-amphetamine occurs exclusively to behaviors mediated by norepinephrine.     

Effect of sleep on nocturnal bronchoconstriction and ventilatory patterns in asthmatics

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.     

D-amphetamine-induced hypothermia and hypermotility in rats: Changes after systemic administration of beta-endorphin

Systemically administered beta-endorphin was tested in rats for its ability to modify the hypothermia and hypermotility induced by d-amphetamine. Colonic temperature and motor activity were measured in a cold (4°C) ambient temperature in animals given IP injections of beta-endorphin (0.1, 1.0, or 3.0 mg/kg), naloxone (10 mg/kg), or morphine (30 mg/kg). The same measurements were taken in animals given beta-endorphin (1.0 mg/kg) in combination with naloxone or saline pretreatment and d-amphetamine (15 mg/kg) or saline post-treatment. Morphine alone had a biphasic effect on thermoregulation, but did not affect d-amphetamine-induced hypothermia. Activity scores were decreased by morphine, in both d-amphetamine and saline treated animals. The thermal response of rats to beta-endorphin alone was variable, depending on dosage, but all 3 dosages partially blocked the hypothermic effect of d-amphetamine. Naloxone blocked the thermal effects of both beta-endorphin and d-amphetamine. Motor activity tended to be decreased by naloxone, regardless of amphetamine treatment, but beta-endorphin tended to increase activity in amphetamine-treated animals and reduce it in saline-treated controls. In their actions on both thermoregulation and activity, naloxone and beta-endorphin appeared to interact independently with d-amphetamine, often producing effects in the same direction, but in combination, they tended to be mutually inhibitory.     

Immune alterations after selective rapid eye movement or total sleep deprivation in healthy male volunteers

We investigated the impact of two nights of total sleep deprivation (SD) or four nights of rapid eye movement (REM) SD on immunological parameters in healthy men. Thirty-two volunteers were randomly assigned to three protocols (control, total SD or REM SD). Both SD protocols were followed by three nights of sleep recovery. The control and REM SD groups had regular nights of sleep monitored by polysomnography. Circulating white blood cells (WBCs), T- (CD4/CD8) and B-lymphocytes, Ig classes, complement and cytokine levels were assessed daily. Two nights of total SD increased the numbers of leukocytes and neutrophils compared with baseline levels, and these levels returned to baseline after 24 h of sleep recovery. The CD4(+) T-cells increased during the total SD period (one and two nights) and IgA levels decreased during the entire period of REM SD. These levels did not return to baseline after three nights of sleep recovery. Levels of monocytes, eosinophils, basophils and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) remained unchanged by both protocols of SD. Our findings suggest that both protocols affected the human immune profile, although in different parameters, and that CD4(+) T-cells and IgA levels were not re-established after sleep recovery.     

Precocious induction of luteal activation and termination of delayed implantation in mink with the dopamine antagonist pimozide

The effects of the dopamine antagonist pimozide on the preimplantation delay phase of mink gestation were investigated in field and laboratory trials. Three doses of 0.1 mg pimozide in acetic acid administered on the 7th, 9th and 11th days after mating abbreviated gestation in Pastel kit female mink to a mean (+/- SEM) of 45.5 +/- 0.5 days, 10 days less than that observed in mink treated with vehicle only (55.6 +/- 0.6 days). In laboratory trials, four doses of 0.1 mg pimozide on the 7th, 9th, 11th and 13th day after mating resulted in embryo implantation at a mean of 25 +/- 4.3 days after mating while vehicle-treated control animals had mean preimplantation delay of 37 +/- 3.1 days. Luteal activation in the pimozide-treated group, as indicated by a rapid increase in circulating progesterone, began within 2 days after the first pimozide injection. No increase was observed in vehicle-treated mink until 6 or more days after the initiation of injections or 13 days after mating. It was concluded that pimozide, presumably by permitting endogenous secretion of prolactin, can induce precocious luteal activation and embryo implantation in the mink.