Prolonged enhancement of REM sleep produced by carbachol microinjection into the amygdala

The effect on sleep organization of carbachol microinjected into different amygdaloid nuclei was analysed in 12 cats. Single carbachol doses of 8 micrograms in 0.50 microliter saline were delivered unilaterally or bilaterally into the central, basal, lateral or basolateral amygdaloid nucleus. Carbachol administration into the central nucleus induced a prolonged (5 days) enhancement of both REM sleep and its preceeding slow wave sleep episodes with PGO waves (sommeil phasique a ondes lentes, SPHOL), which was more pronounced following bilateral than unilateral carbachol administration. However, neither SPHOL nor REM sleep changes were produced by administration of carbachol into the other amygdaloid nuclei. We conclude that cholinergic activation of the central amygdaloid nucleus produces a long-term facilitation of REM sleep occurrence.     

Localization of pontine PGO wave generation sites and their anatomical projections in the rat

A number of experimental and theoretical reports have suggested that the ponto-geniculo-occipital (PGO) wave-generating cells are involved in the generation of rapid eye movement (REM) sleep and REM sleep dependent cognitive functions. No studies to date have examined anatomical projections from PGO-generating cells to those brain structures involved in REM sleep generation and cognitive functions. In the present study, pontine PGO wave-generating sites were mapped by microinjecting carbachol in 74 sites of the rat brainstem. Those microinjections elicited PGO waves only when made in the dorsal part of the nucleus subcoeruleus of the pons. In six rats, the anterograde tracer biotinylated dextran amine (BDA) was microinjected into the physiologically identified cholinoceptive pontine PGO-generating site to identify brain structures receiving efferent projections from those PGO-generating sites. In all cases, small volume injections of BDA in the cholinoceptive pontine PGO-generating sites resulted in anterograde labeling of fibers and terminals in many regions of the brain. The most important output structures of those PGO-generating cells were the occipital cortex, entorhinal cortex, piriform cortex, amygdala, hippocampus, and many other thalamic, hypothalamic, and brainstem nuclei that participate in the generation of REM sleep. These findings provide anatomical evidence for the hypothesis that the PGO-generating cells in the pons could be involved in the generation of REM sleep. Since PGO-generating cells project to the entorhinal cortex, piriform cortex, amygdala, and hippocampus, these PGO-generating cells could also be involved in the modulation of cognitive functions.     

Contributions of the pedunculopontine region to normal and altered REM sleep

The pedunculopontine (PPN) region of the upper brainstem is recognized as a critical modulator of activated behavioral states such as wakefulness and rapid eye movement (REM) sleep. The expression of REM sleep-related physiology (e.g. thalamocortical arousal, ponto-geniculate-occipital (PGO) waves, and atonia) depends upon a subpopulation of PPN neurons that release acetylcholine (ACh) to act upon muscarinic receptors (mAChRs). Serotonin's potent hyperpolarization of cholinergic PPN neurons is central to present working models of REM sleep control. A growing body of experimental evidence and clinical experience suggests that the responsiveness of the PPN region, and thereby modulation of REM sleep, involves closely adjacent glutamatergic neurons and alternate afferent neurotransmitters. Although many of these afferents are yet to be defined, dopamine-sensitive GABAergic pathways exiting the main output nuclei of the basal ganglia and adjacent forebrain nuclei appear to be the most conspicuous and the most likely to be clinically relevant. These GABAergic pathways are ideally sited to modulate the physiologic hallmarks of REM sleep differentially (e.g. atonia versus cortical activation), because each originates from a functionally unique forebrain circuit and terminates in a unique pattern upon brain stem neurons with unique membrane characteristics. Evidence is reviewed that changes in the quality, timing, and quantity of REM sleep that characterize narcolepsy, REM sleep behavior disorder, and neurodegenerative and affective disorders (depression and schizophrenia) reflect 1) changes in responsiveness of cells in the PPN region governed by these afferents; 2) increase or decrease in PPN cell number; or 3) mAChRs mediating increased responsiveness to ACh derived from the PPN. Auditory evoked potentials and acoustic startle responses provide means independent from recording sleep to assess pathophysiologies affecting the PPN and its connections and thereby complement investigations of their role in affecting daytime functions (e.g. arousal and attention).     

Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram

The sleep and waking and EEG power spectrum effects of the putative 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.) were studied alone and in co-administration with the selective serotonin re-uptake inhibitor citalopram (5.0 mg/kg, i.p.) in the rat. Citalopram, as in a prior dose-response study, reduced REM sleep. In addition, a slight increase in NREM sleep was observed. Citalopram reduced NREM fronto-parietal (FP) EEG power density in the 5-20 Hz range. When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration. NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum. When administered in combination with citalopram, an attenuation of the power density reduction in the 7-15 Hz range in the FF EEG of citalopram alone, was observed. However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented. The results are compatible with the notion that serotonin is involved in the modulation of the slow wave activity in the EEG during NREM sleep. The results are cordant with other data suggesting that postsynaptic 5-HT1A stimulation might increase slow wave activity in the NREM EEG, and that serotonergic stimulation of other receptor subtypes (possibly 5-HT2) may decrease slow wave activity in the NREM EEG.     

Chronic low-amplitude electrical stimulation of the laterodorsal tegmental nucleus of freely moving cats increases REM sleep

While cholinergic stimulation of the PRF evokes a REM-like state, electrical stimulation of LDT/PPT neurons has not been used to test the hypothesis of mesopontine cholinergic control of REM sleep. Adult cats were implanted for electrographic recording and with bipolar unilateral stimulating electrodes, either in the LDT or within the PRF (stimulation control). Baseline recordings of the normal sleep-wake cycle were carried out for 5 h. On the next day, continuous stimulation of the LDT or mPRF was carried out during the same time period (0.5 ms pulses, 1 microA, 8 Hz) and with post-stimulation recording for 3 h. A second baseline recording day followed with same protocol as the first baseline day. This 3-day sequence, separated by 3 days, was repeated three times in each of the three LDT and the three medial PRF cats. Five hours of chronic low-amplitude stimulation of the LDT induced a highly significant increase in total REM and in the duration of REM sleep bouts. Stimulation of the mPRF did not affect any of the behavioral states. This study, the first to our knowledge to use low-amplitude stimulation of LDT in freely moving cats, indicates the importance of mesopontine cholinergic neurons in REM sleep.     

Effects of accumbens m-chlorophenylbiguanide microinjections on sleep and waking in intact and 6-hydroxydopamine-treated rats

Effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide (10.0-40.0 microg), on sleep and waking were studied in control, vehicle-treated and 6-hydroxydopamine-injected rats. Bilateral injections of m-chlorophenylbiguanide into the nucleus accumbens of the control and the vehicle-infused animals significantly increased waking and reduced slow wave sleep. Rapid eye movement sleep (REM sleep) remained unchanged. Pretreatment with the selective 5-HT3 receptor antagonist, MDL 72222 (1aH,3a,5a, H-tropan-3-yl-3,5-dichloro-benzoate) (0.5 mg/kg, s.c.), reversed the effects of m-chlorophenylbiguanide (10.0-20.0 microg) on sleep and waking in the control group. Administration of the 5-HT3 receptor agonist to the 6-hydroxydopamine-treated animals modified only slightly the time spent in wakefulness and slow wave sleep, while REM sleep was significantly and dose dependently reduced. Our findings further support the proposal that increase of wakefulness and reduction of slow wave sleep after activation of 5-HT3 receptors, is partly related to the release of endogenous dopamine.     

Influence of sleep states on laryngeal and abdominal muscle response to upper airway occlusion in lambs

This study was aimed at describing abdominal and laryngeal muscle responses to upper airway occlusion (UAO) in early life and the effect of sleep states on these responses. Twelve nonsedated, 9-26-d-old lambs were studied. We simultaneously recorded 1) airflow (pneumotachograph + face mask); 2) sleep states (electrocorticogram and electrooculogram); 3) abdominal muscle (external obliquus) electromyogram (EMG); and 4) glottic constrictor (thyroarytenoid) and dilator (posterior cricoarytenoid and cricothyroid) muscle EMGs. The pneumotachograph was repeatedly occluded for 15-30 s in wakefulness and natural sleep. We analyzed 90 occlusions during wakefulness (11 lambs), 28 during non-rapid eye movement (nREM) sleep (six lambs), and 23 during rapid eye movement (REM) sleep (five lambs). A phasic expiratory external obliquus EMG was present during baseline and progressively increased throughout UAO in wakefulness and nREM sleep, but not in REM sleep. Phasic thyroarytenoid EMG progressively increased during inspiratory efforts throughout UAO in wakefulness and nREM sleep, paralleling the increase in glottic dilator (posterior cricoarytenoid and cricothyroid) EMG. In contrast, glottic muscle response to UAO in REM sleep was severely blunted or disorganized by frequent swallowing movements. We conclude that UAO triggers complex and coordinated laryngeal and abdominal muscle responses during wakefulness and nREM sleep in lambs; these responses are largely absent, however, in REM sleep. These unique results, together with the defective arousal response in REM sleep, suggest that vulnerability to airway occlusion could be increased during REM sleep in early life. Possible implications for understanding severe postnatal apneas are discussed.     

The rat as an experimental model for sleep neurophysiology.

The aim of this study was to develop a sleep-wake recording system for rats that would yield results more comparable to those obtained from cats than those that are usually reported. For 18 male Sprague-Dawley rats, the authors combined measures of cortical and hippocampal electroencephalogram (EEG) and neck muscle electromyogram with the electrooculogram and pontine EEG, so that the behavioral states could be identified with greater confidence with the use of polygraphic criteria developed in the cat and so that the distinctive phasic events of REM sleep could be more easily studied in the rat. The results suggest that for many neurophysiological studies, the rat is a suitable alternative to the cat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Affect intensity and phasic REM sleep in depressed men before and after treatment with cognitive-behavioral therapy.

Explored the relationship between daytime affect and REM sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in a control group of 43 healthy Ss. The intensity of daytime affect (as measured by the sum of positive and negative affects) in depressed men correlated significantly and positively with phasic REM sleep measures at both pre- and posttreatment. This relationship was not found in healthy control Ss. In depressed men, both affect intensity and phasic REM sleep measures decreased over the course of treatment. The results suggest a relationship between phasic REM sleep and intensity of affect reported by depressed men. On the basis of this preliminary observation, it was hypothesized that abnormalities in phasic REM sleep in depressed patients are related, in part, to fundamental alterations in the intensity of their affective experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep and quantitative EEG in patients with progressive supranuclear palsy

Sleep architecture and quantitative EEG from wakefulness and REM sleep were studied in six patients (mean age, 70.5 years) with progressive supranuclear palsy (PSP) and compared with that of six control subjects (mean age, 69.8 years). Particular attention was given to quantifying REM sleep variables because of the known PSP-associated degeneration of the pedunculopontine tegmentum (PPT)--a critical structure in REM sleep generation. Patients with PSP had a shorter total sleep time, a lower sleep efficiency, a drastic reduction in sleep spindles, an atonic slow-wave sleep, and a lower percentage of REM sleep. The lower percentage of REM sleep was the result of both a reduction in the number of REM periods and a reduction in mean period of duration. REM density was also reduced while REM efficiency, atonia, and phasic EMG were similar to control values. REM sleep findings are consistent with the known role of the PPT in REM sleep induction. A slowing of the awake EEG was found for the six frontal leads and for C4, P4, and T4 in PSP patients. The frontal EEG slowing found in wakefulness is in accord with imaging and neuropsychological studies showing impairment of the frontal lobes in these patients. REM sleep EEG was not significantly slower in any regions. Because all previous studies on PSP have relied on visual inspection of the EEG tracings, the present finding of EEG slowing in the frontal lobes (rather than in the temporal regions or diffusely) suggests that our quantitative EEG approach may be more useful in determining specific regions of impaired cortical activity.     

Rapid eye movement sleep correlates with the overall activities of the hypothalamic-pituitary-adrenal axis and sympathetic system in healthy humans

To assess the association of the overall amount of rapid eye movement (REM) sleep and the activities of the hypothalamic-pituitary-adrenal axis and sympathetic system, we performed polysomnography and measured 24-h urinary free cortisol and catecholamine excretion in 21 healthy adults. After an adaptation night, each subject was recorded in the sleep laboratory for 3 consecutive nights while 24-h urine specimens were collected. Urinary free cortisol, epinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid levels were significantly and positively correlated with the average values of percent REM sleep (P < 0.05). There were no correlations between hormone values and REM latency, other variables of REM distribution, or REM density, an index of phasic activity during REM sleep. The positive correlations between stress system activity and REM sleep are consistent with hormonal and sleep alterations in melancholic depression, a state characterized by increased cortisol and catecholamine secretion.     

Behavioral state control through differential serotonergic inhibition in the mesopontine cholinergic nuclei: a simultaneous unit recording and microdialysis study

Cholinergic neurons of the mesopontine nuclei are strongly implicated in behavioral state regulation. One population of neurons in the cholinergic zone of the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as rapid eye movement (REM)-on neurons, shows preferential discharge activity during REM sleep, and extensive data indicate a key role in production of this state. Another neuronal group present in the same cholinergic zone of the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as Wake/REM-on neurons, shows preferential discharge activity during both wakefulness and REM sleep and is implicated in the production of electroencephalographic activation in both of these states. To test the hypothesis of differential serotonergic inhibition as an explanation of the different state-related discharge activity, we developed a novel methodology that enabled, in freely behaving animals, simultaneous unit recording and local perfusion of neuropharmacological agents using a microdialysis probe adjacent to the recording electrodes. Discharge activity of REM-on neurons was almost completely suppressed by local microdialysis perfusion of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), although this agonist had minimal or no effect on the Wake/REM-on neurons. We conclude that selective serotonergic inhibition is a basis of differential state regulation in the mesopontine cholinergic nuclei, and that the novel methodology combining neurophysiological and neuropharmacological information from the freely behaving animal shows great promise for further insight into the neural basis of behavioral control.     

Sleep electroencephalographic abnormalities in adolescent depressives: effects of scopolamine

In contrast to sleep studies of adult depressives that have consistently demonstrated abnormalities of sleep continuity, slow-wave sleep, and REM sleep, existing studies of depressed children and adolescents have been conflicting. Furthermore, only one study has explored the cholinergic regulation of sleep in early-onset depressives. In the present study, the electroencephalographic sleep of 20 adolescent outpatients with major depressive episodes and 13 normal control adolescents was obtained on two separate 2-night sessions, 1 night incorporating challenge with scopolamine. Depressed adolescents showed increased baseline phasic REM sleep measures, increased arousals, a trend toward reduced slow-wave sleep, and a greater difference in the change of first REM period density on the scopolamine night versus placebo night compared to controls. These findings support the continuity of some sleep abnormalities of depression into adolescence, and suggest that adolescent depression may be associated with alterations of cholinergic neurotransmission in some patients.     

Comparative study in the rat of the actions of different types of stress on the release of 5-HT in raphe nuclei and forebrain areas

The effects of several stress procedures on the release of 5-HT in the dorsal and median raphe nuclei (DRN and MRN, respectively) and in forebrain structures of the rat brain innervated by both nuclei have been studied using intracerebral microdialysis. Handling for 30 sec, a saline injection and forced swimming for 5 min elevated significantly the 5-HT output in the MRN. The 5-HT output in the DRN was also enhanced by a saline injection. With regard to the forebrain structure examined, handling and forced swimming increased dialysate 5-HT in the amygdala. The injection of saline induced a slight, but significant, elevation of 5-HT in the medial prefrontal cortex. In contrast, the outflow of 5-HT was significantly reduced in the ventral hippocampus and medial prefrontal cortex following forced swimming and this effect persisted well beyond the cessation of the swim session. These results indicate that the efflux of 5-HT in the MRN appears to respond to different forms of stress, whereas that in the DRN only increases after the injection of saline. The release of 5-HT in the forebrain structures is also dependent on the type of stress procedure and the region studied.     

Increased GABAergic activity in the region of the pedunculopontine and deep mesencephalic reticular nuclei reduces REM sleep and impairs learning in rats.

Newly formed memories are initially fragile and require consolidation to be transformed into an enduring state. Memory consolidation may occur during increased postlearning REM sleep. REM deprivation during these periods (termed REM sleep windows [RSWs]) impairs subsequent performance. The pedunculopontine nucleus (PPT) and adjacent deep mesencephalic reticular nuclei (DpMe) have been implicated in the generation of REM sleep. Following 24-hr baseline recording, rats were trained on the 2-way avoidance task for 50 trials/day over 2 days and retested on Day 3. EEG was recorded 22 hr after training on training Days 1 and 2. Rats were injected with the GABAB agonist baclofen or saline into the PPT/DpMe region at 0300 to coincide with the start of a known RSW. Based on shuttle performance, saline rats were assigned post hoc to a learning group (LG) that avoided the footshock at least 60% at retest or nonlearning group (NLG) that performed below this criterion. Baclofen-injected rats were not assigned post hoc into separate groups as all rats performed below the learning criterion. PPN/DpMe infusions of the inhibitory GABAB agonist baclofen decreased REM and impaired subsequent memory performance. Normal GABAergic transmission in the PPN/DpMe may be necessary for REM to occur and for the consolidation of incentive learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effects of serotonin in the hippocampus and the entorhinal cortex

Among the molecular, cellular, and systemic events that have been proposed to modulate the function of the hippocampus and the entorhinal cortex (EC), one of the most frequently cited possibilities is the activation of the serotonergic system. Neurons in the hippocampus and in the EC receive a strong serotonergic projection from the raphe nuclei and express serotonin (5-HT) receptors at high density. Here we review the various effects of 5-HT on intrinsic and synaptic properties of neurons in the hippocampus and the EC. Although similar membrane-potential changes following 5-HT application have been reported for neurons of the entorhinal cortex and the hippocampus, the effects of serotonin on synaptic transmission are contrary in both areas. Serotonin mainly depresses fast and slow inhibition of the principal output cells of the hippocampus, whereas it selectively suppresses the excitation in the entorhinal cortex. On the basis of these data, we discuss the possible role of serotonin under physiological and pathophysiological circumstances.     

Adenosine A1 receptor agonist GR79236 suppresses apnea during all sleep stages in the rat

We tested the hypothesis that N-[(1S, trans)-2-hydroxycyclopentyl]adenosine (GR79236), a novel adenosine A1 receptor agonist, would suppress sleep-related apnea in the rat at doses not associated with hypotension or hypothermia. Nine adult Sprague-Dawley rats were instrumented for chronic recording of sleep by electroencephalographic and electromyographic monitoring. Respirations were measured by single chamber plethysmograph, and blood pressure and heart period were transduced by a telemetric implant. Each rat was polygraphically recorded for 6 hours on four occasions in random order, with recordings for an individual animal separated by at least 3 days. Fifteen minutes prior to each recording (0945 hours) each animal received a 1 ml/kg intraperitoneal bolus injection of one of four injectates: saline (control) or 0.03 mg/kg, 0.3 mg/kg, or 3 mg/kg of GR79236. The study was a repeated-measures balanced design such that each animal was recorded exactly once for each injectate. The rate of spontaneous apneas (pauses > 2.5 seconds) was significantly reduced during all sleep stages by all doses of GR79236. At the highest dose, apnea index was reduced by over 70% in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In contrast, GR79236 had no effect on sleep stage volumes or blood pressure at any dose tested. Heart rate and core temperature were reduced only at the highest dose (3 mg/kg). We conclude that the adenosine A1 receptor agonist GR79236 significantly suppresses apnea expression in all sleep stages at doses not associated with significant changes in sleep architecture, blood pressure, heart rate, or core temperature.     

Use of dynamic two-dimensional transesophageal echocardiography for renal cell carcinoma with cavoatrial tumor thrombus

Previous investigations involving continuous blood pressure (BP) monitoring have shown an important alteration of the 24-hour BP profile in patients with obstructive sleep apnea syndrome (OSAS). We investigated the impact of REM sleep on the 24-hour BP cycle in 16 severe OSAS male patients (mean respiratory disturbance index = 66 +/- 16 events/hour of sleep), with hypertension (mean BP 162 +/- 21/105 +/- 11 mmHg World Health Organization (WHO) protocol). Two successive nights of polysomnography were performed, and arterial BP was monitored continuously during the second 24-hour period after brachial artery cannulation. During the daytime, subjects were kept awake and supine. At 3 p.m. BP was continuously monitored during quiet supine wakefulness for 20 minutes. Systolic, diastolic and mean BP and heart rate (HR) were analyzed and tabulated in mean values of 5 minute segments. Sleep/wake information were correlated with cardiovascular variables. Each uninterrupted REM sleep period was identified and comparison between the period of quiet supine wakefulness and REM sleep HR and BP values was performed. 8 OSAS patients presented a normal drop of the mean arterial BP during the nocturnal REM sleep periods compared to quiet supine wakefulness (mean value = -10.8 +/- 7.3 mmHg) ("dippers") while the other 8 subjects ("REM sleep non dippers"), revealed an elevated mean arterial BP during REM sleep (mean value = 18.9 +/- 10.9 mm Hg). The absence of the normal circadian BP dip seen during the nocturnal sleep period is considered as an indication of vascular risk. The REM sleep non dipping may play a role in this risk.     

GABA receptors in the dorsal motor nucleus of the vagus influence feline lower esophageal sphincter and gastric function

Gamma-aminobutyric acid (GABA) antagonist (bicuculline methiodide, BIC; picrotoxin, PIC) or agonist (muscimol, MUS) microinjections were made into the dorsal motor nucleus of the vagus nerve (DMV), and effects on lower esophageal sphincter pressure (LESP), gastric motility, and gastric acid secretion were determined in chloralose-anesthetized cats. Right or left DMV sites were microinjected with BIC, PIC, MUS, or isotonic tonic saline (140 nl) through a glass micropipette having a tip diameter of 15-21 microns. Esophageal body, LESP, and gastric fundic pressures were measured manometrically. Circular smooth muscle contractions of the antrum and pylorus were recorded with strain-gauge force transducers. Gastric acid secretion was measured every 15 min through a gastric cannula and titrated to pH 7.0. DMV microinjection sites were verified histologically. Direct BIC microinjections (0.275 or 0.550 nmol) into the DMV primarily produced a decrease in LESP (71% of all sites tested), with mean LESP changing from 23.2 +/- 1.7 mmHg to 3.7 +/- 0.7 mmHg (p < 0.01). Tonic LESP increases and phasic LESP contractile activity occurred less frequently. BIC-induced LESP responses were abolished by vagotomy or by microinjections of MUS (0.5 to 10 nmol) into the DMV. Direct PIC microinjection (0.232 nmol) into the DMV produced a pattern of responses similar to those observed with BIC (which were also abolished by vagotomy or by MUS microinjections into the DMV). The antrum and pylorus were also responsive to DMV microinjections of both GABA antagonists. Microinjections of BIC or PIC into the DMV produced increases in gastric circular muscle activity that occurred less frequently than LESP effects, but also were eliminated by vagotomy. The high (0.550 nmol) dose of BIC increased gastric motility significantly more often than the low dose of BIC (p < 0.05). In addition, BIC (0.550 nmol) microinjections into the DMV increased gastric secretory volume (from 0.6 +/- 0.2 to 6.0 +/- 2.5 ml/15 min; p < 0.01) and total titratible acid (from 34.4 +/- 8.9 to 86.0 +/- 19.1 mEq/15 min; p < 0.01), and decreased gastric pH (from 4.63 +/- 0.44 to 3.50 +/- 0.49; p < 0.05). Vagotomy also eliminated the gastric secretory effects of DMV BIC. Direct microinjections of MUS into the DMV also blocked BIC- or PIC-induced changes in gastric motility and/or gastric acid secretion. Isotonic saline microinjected into the DMV did not increase basal or decrease stimulated gastric esophageal motility or gastric secretion. These data indicate that LESP, gastric motility, and gastric secretion are influenced by a tonic DMV inhibition mediated by GABAA receptor stimulation of the DMV. Because disinhibition of these receptors clearly activates the upper gut, future work should focus on identifying the nuclei providing this synaptic input to the DMV that might be involved in the functional regulation of upper gut motor and secretory function.     

Opioids activate G proteins in REM sleep-related brain stem nuclei of rat

Mu opioid receptors within the pontine reticular formation contribute to opioid-induced rapid eye movement (REM) sleep inhibition. Mu receptors are coupled to guanine nucleotide binding (G) proteins and this study tested the hypothesis that the micro opioid agonist [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) would activate G proteins in rat brain stem nuclei known to regulate REM sleep. In vitro autoradiography of DAMGO-stimulated [35S]GTPgammaS binding showed that, compared with basal [35S]GTPgammaS binding, DAMGO significantly increased G protein activation in the nucleus pontis oralis (56.2%), nucleus pontis caudalis (57.3%), laterodorsal tegmental nucleus (75.8%), pedunculopontine tegmental nucleus (72.4%), nucleus locus coeruleus (77.2%) and dorsal raphe nucleus (73.4%). DAMGO stimulation of [35S]GTPgammaS binding in nuclei regulating REM sleep suggests that opioid-induced REM sleep inhibition involves activation of G proteins.