The D1 dopamine receptor antagonist SCH 23390 enhances REM sleep in the rat

The effect of the D1 dopamine receptor antagonist SCH 23390 on sleep patterns was studied in rats by means of the electroencephalographic (EEG) technique. Haloperidol, an established D2 antagonist neuroleptic, was used for comparison. Over a very small dose range (0.003-0.03 mg/kg, subcutaneously), SCH 23390 significantly increased the time spent in total sleep, including rapid eye movement (REM) and non-REM sleep. The magnitude of the overall change of REM sleep was considerably greater than that of non-REM sleep. Enhancement of the amount of REM was characterized by increase in number of episodes but no change of latency to the first period of REM. Haloperidol increased non-REM sleep at 0.3-3 mg/kg, orally, but did not affect other measures of REM. Considering the small dose range at which SCH 23390 was effective, and the fact that REM and non-REM sleep may be unrelated events, it is suggested that promotion of REM sleep is a specific effect induced by selective blockade of D1 receptors.     

The dopamine D1 receptor is involved in the regulation of REM sleep in the rat

The dopamine D1 receptor agonist, SKF 38393, and the D1 antagonist, SCH 23390, were studied for their effects on sleep in the rat. Over 6 h, SKF 38393 (0.1-10 mg/kg s.c.) dose dependently reduced the amount of rapid eye movement (REM) sleep and enhanced the duration of wakefulness. The drug affected REM at low doses (ED50 = 0.4 mg/kg) at which wakefulness was unchanged and the characteristic grooming behavior was not apparent. REM changes were characterized by a decrease in the number of episodes with no alteration of latency to the first episode. Over a very low dose range (0.003-0.3 mg/kg s.c.), SCH 23390 enhanced the amount of REM by increasing both number and average duration of episodes. There was also a moderate increase of non-REM sleep but the percent change was less marked than that occurring for REM. Given at 0.003 mg/kg, SCH 23390 prevented the REM changes induced by SKF 38393 (0.3-3 mg/kg). It is suggested that D1 receptors are involved in the regulation of the REM sleep process.     

REM sleep deprivation decreases apomorphine-induced stimulation of locomotor activity but not stereotyped behavior in mice.

1. Effects of rapid eye movement (REM) sleep deprivation on central dopaminergic system were investigated by testing the behavioral responses to apomorphine and brain dopamine metabolism in mice. 2. REM sleep deprivation for 48 hr significantly suppressed apomorphine.HCl (3.0 and 6.0 mg/kg, i.p.)-stimulated spontaneous locomotor activity without affecting the intensity of stereotyped behavior. 3. Neither the latency of nociceptive response in a hot-plate test nor the duration of pentobarbital-induced sleep was changed by REM sleep deprivation. 4. Dopamine turnover in the striatum and the nucleus accumbens of REM sleep-deprived mice was significantly higher than that of control animals. 5. These results suggest that REM sleep deprivation may decrease the function of postsynaptic dopamine receptor in the mesolimbic but not nigrostriatal dopaminergic system.     

Effects of biperiden on sleep at baseline and after 72 h of REM sleep deprivation in the cat

We examined the effects of the muscarinic M1 antagonist biperiden in cats. In the first experiment a dose-response analysis was performed with intraventricular injection (IV ventricle) of biperiden. In the second experiment after REM sleep deprivation cats were injected with either biperiden (0.1 mg/kg) or saline. Biperiden produced a reduction in REM sleep percentage and an increase in REM sleep latency with these high doses. The 0.1 mg/kg biperiden dose, which did not suppress REM sleep at baseline, did reduce the REM sleep rebound. The present study suggests a modulatory role of biperiden on REM sleep regulatory processes. The fact that an effect of biperiden is noted only at the high doses suggests that at these doses the drug is influencing non-M1 receptors. Changes in the sensitivity of these receptors as a result of REM sleep deprivation might explain why a dose of biperiden will reduce REM sleep rebound, while being ineffective in suppressing REM sleep at baseline.     

Effects of the selective dopamine D-2 receptor agonist, quinpirole on sleep and wakefulness in the rat

The effects of the dopamine D-2 receptor agonist, quinpirole, were compared with those produced by dopamine D-2 antagonist, YM-09151-2, in rats implanted with electrodes for chronic sleep recordings. Quinpirole (0.015-1.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness and increased sleep, while higher doses induced the opposite effects. At 0.015 mg/kg, YM-09151-2 slightly augmented wakefulness, while at 1.0-2.0 mg/kg it significantly increased light sleep but depressed REM sleep. Pretreatment with YM-09151-2 in a dose which preferentially acts at presynaptic sites reversed the suppressant effects of a low dose of quinpirole on wakefulness and slow wave sleep. In contrast, the administration of YM-09151-2 in a dose which blocks postsynaptic D-2 receptors prevented the effect of a high dose of quinpirole on wakefulness and slow wave sleep; the depression of REM sleep was not affected. The opposite effects observed on the waking EEG after activation of either dopamine autoreceptors or postsynaptic D-2 receptors with adequate doses of quinpirole tend to indicate an active role for DA in the control of the waking state.     

The dopaminergic system plays a role in the effect of lithium on inhibitory avoidance memory in mice

The effects of dopaminergic drugs on the inhibitory avoidance memory affected by lithium were examined in the Naval Medical Research Institute (NMRI) mice using a single-trial step-down inhibitory (passive) avoidance task. The results showed that post-training administration of lithium (10 mg/kg, i.p.) decreased the step-down latency on the test day, which was fully or partly reversed by pre-test administration of the same dose of the drug; suggesting state-dependent learning induced by lithium. Our results also showed that pre-test (i.p.) administration of the dopamine D1 receptor agonist SKF38393 and the dopamine D2 receptor agonist quinpirole by themselves and in combination with ineffective doses of lithium (0.3, 0.6 and 1.25 mg/kg) reversed the decrease of the step-down latency induced by post-training lithium. In contrast, pre-test administration of the dopamine D1 receptor antagonist SCH23390 (0.025, 0.05 and 0.1 mg/kg, i.p.) and the dopamine D2 receptor antagonist sulpiride (6.25 and 12.5 mg/kg, i.p.) alone or in combination with pre-test lithium (10 mg/kg), did not significantly alter the step-down latency on the test day, except for a higher dose of sulpiride (25 mg/kg) which by itself increased the step-down latency. Furthermore, pre-test administration of a lower dose of sulpiride (3 mg/kg) in combination with ineffective doses of lithium (03, 0.6 and 1.25 mg/kg) also reversed the decrease in the step-down latency induced by post-training lithium. In conclusion, the dopamine D1 and D2 receptor mechanism(s) may be involved, at least partly, in the effect of lithium on retrieval of the inhibitory avoidance memory influenced by the drug.     

Sleep during acute dopamine D1 agonist SKF 38393 or D1 antagonist SCH 23390 administration in rats

The effect of the D1 dopamine (DA) receptor agonist SKF 38393 was compared with that produced by the D1-receptor antagonist, SCH 23390, in rats implanted with electrodes for chronic sleep recordings. SKF 38393 (0.1 to 4.0 mg/kg) significantly suppressed rapid-eye-movement sleep (REMS) after the highest dose. SCH 23390 (0.1 to 2.0 mg/kg) increased slow-wave sleep (SWS), whereas wakefulness (W) and REMS were decreased. Pretreatment with SKF 38393 (0.5 mg/kg) prevented the effects of SCH 23390 (0.25 mg/kg) on W and SWS. However, REM sleep showed a further depression. Pretreatment with SKF 38393 (2.0 mg/kg) or SCH 23390 (0.25 mg/kg) failed to modify the increase of SWS and decrease of W induced by D2 receptor agonist bromocriptine (0.5 mg/kg) in a dose that selectively stimulates DA autoreceptors. On the other hand, SCH 23390 (0.25 mg/kg) failed to prevent REMS depression induced by bromocriptine (6.0 mg/kg) in a dose that preferentially acts at postsynaptic sites. Pretreatment with SCH 23390 (0.25 mg/kg) prevented the increase of W and decrease of SWS induced by the 5-HT2 receptor agonist DOI (0.25 mg/kg). Given the "fragility" of REMS in the rat, nonspecific factors could be contributing to its depression after SKF 38389 or SCH 23390 administration. Inhibition of D1 receptors could be responsible for SCH 23390-induced increase of SWS and decrease of W. However, a blockade of 5-HT2 receptors could be partly involved in these effects. Neither SKF 38393 nor SCH 23390 exerted activity on the sleep-wake cycle, which could be considered to reflect effects at DA autoreceptors.     

Repeated administrations of dopamine receptor agents affect lithium-induced state-dependent learning in mice

The influence of repeated administration of dopamine receptor agents on the effect of lithium on lithium-induced state-dependent learning was examined in mice. Immediate post-training intraperitoneal (i.p.) administrations of lithium (10 and 20 m/kg) decreased the step-down latency of a single-trial inhibitory avoidance task. This was fully or partly reversed by pre-test administration of the same doses of the drug, with maximum response at the dose of 10 mg/kg, suggesting state-dependent learning was induced by lithium. Here, it has also been shown that repeated intracerebroventricular administrations of a mixed D1/D2 dopamine receptors agonist apomorphine (once daily injections of 0.5 microg/mouse for three consecutive days followed by five days of no drug treatment) increased the effect of lower doses of pre-test lithium (1.25, 2.5 and 5 mg/kg, i.p.) on the reinstatement of the step-down latency decreased by post-training lithium (10 mg/kg). On the contrary, not only repeated administrations of the dopamine D1 receptor antagonist SCH 23390 (0.5 and 1 microg/mouse) but also the dopamine D2 receptor antagonist sulpiride (0.3 and 1 microg/mouse) disrupted the state-dependent learning induced by lithium. These results suggest that state-dependent learning induced by lithium may be altered by repeated pretreatment of dopamine receptor agents.     

Effects of N-cyclopentyladenosine and caffeine on sleep regulation in the rat

To study the role of adenosine in sleep regulation, the adenosine A₁ receptor agonist N⁶-cyclopentyladenosine (CPA) and the antagonist caffeine were administered to rats. Intraperitoneal (i.p.) CPA 1 mg/kg but not 0.1 mg/kg, suppressed rapid-eye-movement (REM) sleep and enhanced electroencephalographic (EEG) slow-wave activity (power density 0.75–4.0 Hz) in non-REM sleep. The latter effect was remarkably similar to the response to 6-h sleep deprivation. The effects persisted when CPA-induced hypothermia was prevented. Caffeine (10 and 15 mg/kg i.p.) elicited a dose-dependent increase in waking followed by a prolonged increase of slow-wave activity in non-REM sleep. The combination of caffeine (15 mg/kg) and sleep deprivation caused less increase in slow-wave activity than sleep deprivation alone, indicating that caffeine may reduce the buildup of sleep pressure during waking. The results are consistent with the involvement of adenosine in the regulation of non-REM sleep.     

Endomorphins 1 and 2 induce amnesia via selective modulation of dopamine receptors in mice

The involvement of dopamine receptors in the amnesic effects of the endogenous micro-opioid receptor agonists endomorphins 1 and 2 was investigated by observing step-down type passive avoidance learning in mice. Although the dopamine D1 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (R(+)-SKF38393) (0.05 and 0.1 mg/kg), the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (R(+)-SCH23390) (2.5 and 5 microg/kg) or the dopamine D2 receptor agonist N-n-phenethyl-N-propylethyl-p-(3-hydroxyphenyl)-ethylamine (RU24213) (0.3 and 1 mg/kg) had no significant effects on the endomorphin-1 (10 microg)- or endomorphin-2 (10 microg)-induced decrease in step-down latency of passive avoidance learning, (-)-sulpiride (10 mg/kg), a dopamine D2 receptor antagonist, significantly reversed the decrease in step-down latency evoked by endomorphin-2 (10 microg), but not by endomorphin-1 (10 microg). Taken together, it is likely that stimulation of dopamine D2 receptors results in the endomorphin-2-but not endomorphin-1-induced impairment of passive avoidance learning.     

R278995/CRA0450, a corticotropin-releasing factor (CRF(1)) receptor antagonist modulates REM sleep measures in rats: Implication for therapeutic indication

Abnormalities in the regulation of the hypothalamic stress hormone corticotropin-releasing factor (CRF) are thought to play a critical role in mood disorders. Consequently, CRF receptor antagonists have been proposed as potential novel therapeutic agents of these conditions. Sleep disturbance is common in depressed patients and changed sleep-wake architecture is considered as potential predictor or surrogate marker of response to treatment. The aim of our study was to characterise the effects of oral administration of the corticotropin-releasing factor CRF(1) receptor antagonist R278995/CRA0450 (3 and 10mg/kg) on sleep-wake organization and electroencephalographic (EEG) components in Sprague-Dawley rats, and to determine whether the changes observed in the sleep-EEG pattern resemble those seen with antidepressants. At 3mg/kg, R278995/CRA0450 produced minor changes in sleep behaviour, while an overall reduction in power spectra was observed during deep slow wave sleep. At 10mg/kg, R278995/CRA0450 consistently reduced rapid eye movement (REM) sleep (-75.4%) and increased the REM sleep onset latency (+67%, 92.1±4.9min for vehicle vs. 153.8±24min for R278995/CRA0450), in the absence of systematic changes in spectral EEG pattern, which are characteristic anti-depressant-like effects. These findings in rats indicate that the corticotropin-releasing factor CRF(1) receptor antagonist R278995/CRA0450 is centrally active under standard conditions as it inhibits REM sleep and promotes wakefulness. The characteristic changes found in the sleep EEG model further support the hypothesis that R278995/CRA0450 could exert a non-sedative, antidepressant-like action.     

Role of spinal 5-HT receptors in cutaneous hypersensitivity induced by REM sleep deprivation

Previous studies indicate that rapid eye movement (REM) sleep deprivation facilitates pain sensitivity. Since serotoninergic raphe neurons are involved both in regulation of sleep and descending pain modulation, we studied whether spinal 5-HT receptors have a role in sleep deprivation-induced facilitation of pain-related behavior. REM sleep deprivation of 48h was induced by the flower pot method in the rat. The pain modulatory influence of various serotoninergic compounds administered intrathecally was assessed by determining limb withdrawal response to monofilaments. REM sleep deprivation produced a marked hypersensitivity. Sleep deprivation-induced hypersensitivity and normal sensitivity in controls were reduced both by a 5-HT(1A) receptor antagonist (WAY-100635) and a 5-HT(2C) receptor antagonist (RS-102221). An antagonist of the 5-HT(3) receptor (LY-278584) failed to modulate hypersensitivity in sleep-deprived or control animals. Paradoxically, sensitivity in sleep-deprived and control animals was reduced not only by a 5-HT(1A) receptor antagonist but also by a 5-HT(1A) receptor agonist (8-OHDPAT). The results indicate that serotoninergic receptors in the spinal cord have a complex role in the control of sleep-deprivation induced cutaneous hypersensitivity as well as baseline sensitivity in control conditions. While endogenous serotonin acting on 5-HT(1A) and 5-HT(2C) receptors may facilitate mechanical sensitivity in animals with a sleep deprivation-induced hypersensitivity as well as in controls, increased activation of spinal 5-HT(1A) receptors by an exogenous agonist leads to suppression of mechanical sensitivity in both conditions. Spinal 5-HT(3) receptors do not contribute to cutaneous hypersensitivity induced by sleep deprivation.     

Effects of gamma-oryzanol on gastric lesions and small intestinal propulsive activity in mice

Effects of gamma-oryzanol were studied on gastric lesions induced by both conditioned emotional stimuli (CES) and REM sleep deprivations and on the facilitation of small intestinal propulsive activity by CES in mice. The CES were given by the communication box method, and the REM sleep deprivations were performed by a modified flower pot method. The incidence of gastric lesions in responder mice induced by CES was reduced by twice p.o. administrations at 6 hr interval of gamma-oryzanol at 200 and 500 mg/kg, oxazolam at 2 mg/kg and atropine at 1-10 mg/kg. The incidence in sender mice was also reduced by gamma-oryzanol at 200 and 500 mg/kg. In addition, the incidence of gastric lesions induced by REM sleep deprivation was also reduced by single administration of gamma-oryzanol at 100 and 200 mg/kg and oxazolam at 5 mg/kg. The facilitation of small intestinal propulsive activity in responder mice induced by CES was suppressed by gamma-oryzanol at 100 and 200 mg/kg and atropine at 10 mg/kg. These results indicate that gamma-oryzanol has an antiulcerative action on gastric lesions induced by CES and REM sleep deprivation, and it has a suppressive action on the facilitation of intestinal propulsion induced by CES.     

Biphasic effects of dopamine D-2 receptor agonists on sleep and wakefulness in the rat

The effects of the dopamine (DA) receptor agonists apomorphine, bromocriptine and pergolide were compared with those produced by a DA receptor antagonist, haloperidol, in rats implanted with electrodes for chronic sleep recordings. Apomorphine (0.025–2.0 mg/kg) and bromocriptine (0.25–6.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness (W) and increased slow wave sleep (SWS) and REM sleep (REMS), while large doses induced opposite effects. The effects of pergolide (0.05–0.5 mg/kg) on W and SWS were also biphasic, while REMS was suppressed over the range of dosages given. At 0.040 mg/kg, haloperidol increased W, while at 0.160 mg/kg it produced the opposite effect. Pretreatment with haloperidol (0.020 mg/kg) in a dose which preferentially acts at presynaptic sites reversed the effects of low doses of apomorphine, bromocriptine or pergolide on sleep and W. However, the compound differed substantially in its ability to block agonist effects.The increase in sleep after low doses of apomorphine, bromocriptine or pergolide could be related to activation of presynaptic D-2 receptors located on DA axons of mesolimbic and mesocortical systems. In addition, inhibition of norepinephrine and acetylcholine neurons having inhabitory D-2 receptors could contribute to the increase of sleep after small doses of the DA agonists.     

Serotonin receptor activation in rats previously deprived of REM sleep

The effects of serotonin precursors (L-5-hydroxytryptophan and L-tryptophan, with or without MAO inhibitors) and of agonists (quipazine and 5-methoxy-N,N-dimethyltryptamine-MeO-DMT) were studied in 3 day REM-deprived or control rats, by recording the presence of the serotonin syndrome and the number of head shakes. The REM sleep-deprived rats showed a larger incidence of the serotonin syndrome and a greater number of head shakes in comparison to the control animals, when challenged with the serotonin precursors. Conversely, REM sleep deprivation did not modify the responsiveness of rats to 0.75-6.0 mg/kg of MeO-DMT and to 2.4-6.0 mg/kg of quipazine. However, REM-deprived rats reacted less than controls to 0.3-1.25 mg/kg of quipazine. Increased turnover due to REM sleep deprivation could explain the augmented responsiveness of the rats to the serotonin precursors. Conversely, the decreased responsiveness to quipazine could result from receptor hyposensitivity due to intense receptor activation, caused by the increased turnover, during the 3 day period of REM sleep deprivation.     

5-HT_(1A)和5-HT_2受体功能与觉醒、睡眠成分关系的研究

目的　观察 5 HT1A受体激动剂 8 OH DPAT和HT2受体拮抗剂利坦色林 (ritanserin)对大鼠清醒和睡眠成分的影响 ,给予 5 HT1A受体激动剂和剥夺REM睡眠后皮层 5 HT2 受体结合能力的变化 ,进一步分析两种 5 HT受体亚型之间的关系以及 5 HT2 受体在睡眠中的作用。方法　利用大鼠睡眠自动分析系统定量分析清醒和睡眠成分的变化 ,注射PCPA制作剥夺睡眠的大鼠模型 ,水上平台法制作剥夺REM睡眠的大鼠模型 ,利用放射配体结合实验研究配体与受体结合力的变化。结果　 8 OH DPAT小剂量 (0 0 1mg·kg-1,sc)可以增加深睡眠和浅睡眠 ,减少觉醒 ;大剂量(0 375mg·kg-1,sc)则增加觉醒 ,减少全部睡眠成分。 5 HT2 受体拮抗剂ritanserin可以明显增加深睡眠 ,减少觉醒和REM睡眠。而 8 OH DPAT低剂量与ritanserin联合用药则使深浅睡眠明显增加 ,清醒和REM睡眠明显减少 ,具有协同作用。对于PCPA化使 3种睡眠成分均明显减少 ,觉醒比例明显增加的大鼠 ,ritanserin仅使浅睡眠增加其它成分不变。用 [3 H] ritanserin放射性配基结合显示 ,剥夺大鼠REM睡眠后皮层 5 HT2 受体Bmax值明显增加但Kd 值无变化 ;给予 5 HT1A激动剂 8 OH DPAT后皮层 5 HT2 受体Kd 和Bmax均降低。结论　 5 HT1A受体和 5 HT2 受体与睡眠有密切关系     

Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats

In the present study, we investigated hypnotic activities of chamomile and passiflora extracts using sleep-disturbed model rats. A significant decrease in sleep latency was observed with chamomile extract at a dose of 300 mg/kg, while passiflora extract showed no effects on sleep latency even at a dose of 3000 mg/kg. No significant effects were observed with both herbal extracts on total times of wakefulness, non-rapid eye movement (non-REM) sleep and REM sleep. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3 mg/kg showed a significant antagonistic effect on the shortening in sleep latency induced by chamomile extract. No significant effects were observed with chamomile and passiflora extracts on delta activity during non-REM sleep. In conclusion, chamomile extract is a herb having benzodiazepine-like hypnotic activity.     

Differential effects of the 5-HT1A receptor agonist flesinoxan given locally or systemically on REM sleep in the rat

The effects of flesinoxan, a selective 5-HT1A receptor agonist on spontaneous sleep, were studied in adult rats implanted for chronic sleep recordings. Flesinoxan was administered systemically or infused directly into the dorsal raphe nucleus, the left laterodorsal tegmental nucleus or the medial pontine reticular formation. Systemic administration of flesinoxan (0.03 and/or 0.06 micromol/kg) significantly increased wakefulness and sleep latencies, and reduced rapid eye movement (REM) sleep and the number of REM periods, during the first and/or second 2-h period after treatment. Direct infusion of the 5-HT1A receptor agonist (0.06 and/or 0.12 nmol) into the dorsal raphe nucleus induced a significant increment of REM sleep and augmented the number of REM periods during the second and/or third 2-h period of recording. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the laterodorsal tegmental nucleus reduced REM sleep and the number of REM periods, and augmented REM sleep latency during the first, second and/or third 2-h recording period. Finally, direct infusion of flesinoxan (0.48 nmol) into the medial pontine reticular formation decreased REM sleep and the number of REM periods, and increased REM sleep latency during the first and second 2 h of recording. Our results indicate that the 5-HT1A receptor is involved in the inhibitory effect of serotonin on brainstem structures that act to promote and to induce REM sleep.     

Scopolamine during the paradoxical sleep window impairs radial arm maze learning in rats

It has been proposed that there are paradoxical sleep windows (PSW) during which REM sleep is required for effective learning. Thus, rats deprived of REM sleep during 0-4 (but not 5-8) h after training show impaired learning of a radial maze task. As cholinergic (ACh) systems are active during REM sleep and may be involved in learning, this experiment investigated the effects on learning of pharmacological manipulation of the cholinergic system during the period identified as the PSW. Sprague-Dawley rats were randomly assigned to groups that were physically deprived of REM for 4 h either immediately after training or beginning 4 h after training or treated with the ACh receptor antagonist scopolamine (0-0.4 mg/kg at 0 and 2 h after training or 0.006 mg/kg at 4 and 6 h after training) on each of 9 days of radial maze training. Post-training REM deprivation (0-4 h but not 5-8 h after training) and scopolamine dose-dependently impaired learning. Results suggest that REM sleep and intact ACh neurotransmission are required during the PSW for rats to learn the radial maze task.     

Chronic lithium prevents REM sleep deprivation-induced increased responsiveness to apomorphine

REM sleep deprivation of rats induces an increased responsiveness to dopaminergic agonists. Chronic lithium (Li) has been reported to prevent the development of dopamine receptor supersensitivity induced by other agents. The effects of chronic dietary Li administration (producing a mean serum level of 0.96 mequiv. litre-1) and 96 h REM sleep deprivation were studied. Chronic Li completely blocked the increased stereotypy, and partially prevented the aggressive behaviour induced, respectively, by 0.6 and 5 mg kg-1 of apomorphine in REM sleep deprived rats compared with the appropriate control groups. This study constitutes the first attempt to evaluate chronic lithium effects on rats undergoing REM sleep deprivation, chosen as another method of inducing alteration of dopaminergic sensitivity.