Paradoxical Phase Of Sleep Research Articles

Effect of proline-containing oligopeptides on peculiarities of operant conditioning of behavior in outbred rats

Effect of proline-containing oligopeptides on peculiarities of operant conditioning of behavior in outbred rats

Effects of slow-wave sleep fragmentation and rapid eye movement sleep fragmentation on melatonin secretion

To compare the effect of stage 3 fragmentation and the paradoxical phase of night sleep on melatonin (MT) secretion, and to evaluate the effects of changes in autonomic balance and activation reactions that occur in the orthodox and paradoxical phases of sleep. Fifteen healthy men participated in three sessions: with stage 3 fragmentation, with fragmentation of paradoxical sleep, and in a control experiment in which sleep was not disturbed. In each experiment, 7 saliva samples were collected in the evening, at night and in the morning and the MT content was determined. Heart rate variability was analyzed using an electrocardiogram and autonomic balance was assessed. Sleep fragmentation was accompanied by activation reactions and reduced the duration of stage 3 and paradoxical phase sleep by 50% and 51% in the corresponding sessions. Fragmentation of paradoxical sleep also led to an increase in the duration of night wakefulness. Sleep disturbances caused an increase in MT secretion in the second half of the night and in the morning, especially pronounced in sessions with fragmentation of paradoxical sleep, in which upon awakening MT was 1.8 times higher than in the control. Stage 3 fragmentation was accompanied by increased sympathetic activation, while fragmentation of paradoxical sleep did not cause autonomic shifts. The subjects were divided into 2 clusters: with high and low MT in night and morning saliva samples. In all sessions, subjects with high MT had 1.7-2 times longer duration of night wakefulness; in sessions with fragmentation, they had significantly more activations in the paradoxical phase of sleep. Night sleep disturbances cause an increase in MT secretion, especially pronounced during the fragmentation of the paradoxical phase. An increase in MT levels does not depend on changes in autonomic balance and is apparently associated with activation of the serotonergic system, which accompanies disturbances in the depth and continuity of sleep.

COMORBID DISORDERS OF THE SLEEP CYCLE – AWAKENESS IN KINDLING RATS UNDER THE CONDITIONS OF USING THE H₃ RECEPTOR ANTAGONIST PITOLISANT

Studies of the neuropathophysiological mechanisms of chronic epileptic activity, whicharise with the participation of the endogenous histaminergic system of the brain, allowus to justify effective complex means of controlling both convulsive manifestations andcomorbid states, which include sleep and wakefulness disorders.Aim of the work – to study the characteristics of the sleep-wake cycle in rats with PTZinduced kindling under the condition of using the H3 receptor antagonist pitolisant.Methods. The kindling syndrome was induced in Wistar rats by daily administration ofpentylenetetrazole (PTZ) (35.0 mg/kg, i. p.) for three weeks. In rats in the course of kindlingdevelopment, pitolisant (5,0 mg/kg, i. p.) was used for 30 min before epileptogen administration.Research results. In rats with developed kindling, the paradoxical sleep phase wasreduced to 7,1% of the total observation period (4 hours) and its fragmentation increased39,7% and the latent period of paradoxical sleep was 24,0% less compared to the controlgroup (P<0,05). Pitolizant treatment was accompanied by an increase in the durationof the awake phase, which was 29% of the total observation time (P>0,05). At the sametime, the duration of paradoxical sleep was 11,6% (P>0,05), and the slow-wave sleepphase was 71,0% (P>0,05). The number of sleep-wake cycles unreliably exceeded theindicator in the control group 17,2% (P>0,05). Latent periods of falling asleep exceededthe indicator in the control group 44,1% (P<0,05) and at the same time was higher thanin kindling rats 60,2% (P<0,05). The latency period of paradoxical sleep was 34.2%higher than kindling rats (P<0.05). 
 Conclusions. The formation of PTZ-kindling is accompanied by a reduction in the latent period of emergence and the total duration of the paradoxical phase of sleep, as well as an increase in its fragmentation. Blocking of H3 histamine receptors by pitolisan during the formation of kindling by administration of pentylenetetrazol prevents the occurrence of wake-sleep cycle disorders.

Modulating effect of liposomal miR-101 on the processes of amyloidogenesis, smell, sleep and neuroinflammation in experimental Alzheimer's disease

The current therapy for Alzheimer's disease does not give patients a chance of recovery. Therefore, it is relevant to study the novel factors of influence, in particular microRNA, on the pathogenic mechanisms of amyloidosis. The aim of this work was to determine the effect of miR-101 on early predictors of amyloidosis in experimental Alzheimer's disease in animals. The study was carried out on 25 male rats of 14 months of age. A model of Alzheimer's disease was created by intrahippocampal administration of Aβ40 aggregates to animals. Ten days later, a 10-day course of nasal administration of miR-101 in liposomes was launched. The level of endogenous Aβ42 and cytokines (TNFα, IL-6 and IL-10) was determined in the supernatants of the nerve tissues of the target brain structures (hippocampus, olfactory bulbs, and olfactory tubercles). A neuroethological method of presenting smells of isovaleric acid and peanut butter was used to assess the olfactory system functional state in the experimental rats. In the course of polygraphic registration of the sleep-wakefulness cycle, the representation of wakefulness and individual sleep phases, as well as proportion of incomplete and complete sleep cycles were determined. It was shown that injection of Aβ40 aggregates into the hippocampus simulates an amyloidogenic state in the rat’s hippocampus and olfactory tubercles, but not in the olfactory bulbs. Moreover, a pro-inflammatory state was registered in the hippocampus of the animal brain (an increase in the concentration of pro-inflammatory cytokines TNFα and IL-6), while the cytokine level in the olfactory bulbs and tubercles did not change. When studying the functional state of olfactory analyzers in the rats with Alzheimer's disease, we revealed negative changes in behavioral response to the smell of isovaleric acid and peanut butter. In terms of somnograms, the Aβ40 toxicity caused reduction in the deep slow-wave sleep stage combined with deficiency of the paradoxical sleep phase, and predominance of incomplete sleep cycles. Nasal therapy with miR-101 in liposomes normalized the level of Aβ42 in the hippocampus and olfactory tubercles and decreased the level of proinflammatory cytokines in the hippocampus. MiR-101 prevented olfactory disfunctions in assessing smells of isovaleric acid and peanut butter, increased the ratio of deep slow-wave sleep and paradoxical sleep in the cycle structure and restored proportion of complete sleep cycles in animals. Thus, liposomal miR-101 has an anti-amyloidogenic and anti-inflammatory effect in rats with a model of Alzheimer's disease. It helps to restore the functional state of olfactory analyzer and optimize structural organization of the sleep-wakefulness cycle in sick animals.

Hippocampal theta rhythm induced by rostral pontine nucleus stimulation in the conditions of pedunculopontine tegmental nucleus inactivation

Theta rhythm in rat hippocampus occurs during cortical activation in different forms of waking as well as during paradoxical phase of sleep. The multi-level regulatory system of theta, based mainly on cholinergic transmission, includes structures from the forebrain to the medulla. Among them the most important are two reticular nuclei: the pedunculopontine tegmental nucleus (PPN) and rostral pontine tegmental nucleus (RPO). Functional relations between these two nuclei are still unidentified. It is known that cholinergic stimulation of these nuclei with carbachol leads to induction of theta in the hippocampus. Electrical stimulation has the same effect but only when applied to the RPO. In our experiments, performed on urethanized rats, each of these two methods was applied to the RPO with the PPN being inactivated in the contralateral hemisphere. We found that inactivation of the PPN does not suppress theta induced with carbachol microinjection into the RPO, but completely blocks theta induction with electrical stimulation of the RPO. The results suggest the important role of the PPN in theta rhythm generation from brainstem level, depending on the method of theta rhythm induction, i.e. cholinergic or electric stimulation of the RPO.

1499 – Neurodynamic patterns of sleep disturbances related to posttraumatic stress disorder in war veterans

Sleep disturbances are important features of posttraumatic stress disorder (PTSD), however, data characterizing PTSD sleep phenomena are limited. Detailed clinical description of sleep function and its study with the use of modern instrumental methods is important for timely and differential diagnosis of mental disorders in PTSD patients. 21 war veterans fighting in “hot spots were observed during treatment in the specialized department of psychological rehabilitation, Samara Regional Clinical Hospital for War Veterans. After clinical interview the overnight polysomnography “Sagura-2000” (PSG) was performed. Sleep disorders in PTSD patients are characterized by the complex of subjective, clinical and neurophysiological symptoms: 1. Superficial sleep (restless, lack of deep sleep); 2. Increased motor activity during sleep (number of activations of the paradoxical phase of sleep to those of deep sleep); 3. Nightmares; 4. Specific (defensive) movements during sleep; 5. Frequent nocturnal awakening (increased number and duration of awakenings); 6. The excess of REM sleep. PSG identified the most frequently related nightmares neurodynamic phenomena: 1. Deficiency of the deep sleep (stages 3 and 4 NREM); 2. Up to 70% of the time NREM takes stage 2 sleep; 3. The increase in motor and EEG activations; 4. The number of activations of the REM than those of NREM; 5. The increase in total REM sleep time; 6. Increasing episodes of REM sleep. Further studies are required to clarify polysomnographic sleep changes, in particular, role of REM sleep dysregulation and treatment of sleep disorders in PTSD. Study was supported by Russian Humanitarian Scientific Foundation (???? 12-36-01155)

Characteristics of integrative brain activity during various stages of sleep and in transitional states

Electropolygraphic study of natural night sleep was performed in 16 adult subjects using correlation, coherent, cluster, and factor analyses. New evidence testifies to the active nature of sleep, which is especially manifest during falling asleep and transition from one stage of sleep to another. Falling asleep and deepening the sleep proved to be accompanied by intense reorganization of the cortico-subcortical relationships, which is reflected in the dynamics of cross-correlative and coherent interrelationships of the brain’s bioelectric potentials. Transition from wakefulness to sleep is a heterogeneous process, which is expressed in significant changes in the weights of factors I, II and III of the vector image of multichannel EEG at stage I (B) of sleep, which might reflect changes in the contribution of the main integrative brain system in the reorganization of the brain’s integrated activity. A considerable increase in the weight of factor I (this reflects generalized the modulating effect of the brainstem on the cortex) and a decrease in the weights of factors II and III (which are related to fronto-occipital and interhemispheric interactions) testify to the special synchronizing role of the brainstem in the development of this initial stage of sleep. Deeper sleep is accompanied by a decrease in interhemispheric EEG relationships of the anterior and inferior frontal areas of the cortex, which suggests that coordinated inactivation of the cortex in both hemispheres leads to reorganization of the activity in the frontal areas. Analysis of the average variance of cross-correlative (CC) EEG relationships demonstrates that stability of the spatial structure of interrelationships between various areas of the brain cortex increases with falling asleep at stage I (A); however, during transition to stage I (B), the CC EEG values become unstable and, with deepening sleep, the variance of these values decreases in the frontal brain cortex. With the onset of the paradoxical phase of sleep, the variance of the levels of interregional interactions increases to the maximum, especially with respect to the EEG relations of the posteriotemporal and inferiofrontal areas of both hemispheres.

To what extent is sleep rebound effective in reversing the effects of paradoxical sleep deprivation on gene expression in the brain?

Sleep is essential to maintaining health and well-being. It has been demonstrated that some of the biological alterations caused by paradoxical sleep deprivation (PSD) are not completely reversed after a period of sleep rebound (SR). The purpose of this study was to determine to what extent the specific molecular changes that occur in the rat cerebral cortex after 96 h of PSD can effectively be reversed during 24 h of recovery. Total RNA from the right cerebral cortex of Wistar male rats and GeneChip ® Rat Genome 230 2.0 arrays were used to perform comprehensive microarray analysis of gene expression in control, PSD and SR groups. Microarray data were validated by Real Time qPCR. A total of 78 unique transcripts were differently expressed after PSD relative to control levels. These include genes related to metabolic processes, the circadian sleep–wake cycle, response to stimuli, regulation of cell proliferation and signaling pathways. After 24 h of sleep rebound, ∼62% of the sleep deprivation transcripts were again detected as differently expressed in the SR relative to the PSD group, although in the opposite direction. On the other hand, the expression of the remaining transcripts showed intermediate values between control and sleep-deprived animals. In summary, our results provide a unique set of transcripts that might be specific related to regulation of paradoxical sleep phase and sleep homeostasis processes, as well as to the biological basis of sleep disorders.

The role of the medial preoptic area of the hypothalamus in organizing the paradoxical phase of sleep.

Chronic experiments were performed on cats to study the effects of electrical stimulation of the medial preoptic area of the hypothalamus on the latent period, duration, and structure of paradoxical sleep, as well as the dynamics of neuron activity in this structure during the sleep-waking cycle. These investigations showed that low-frequency stimulation of the medial preoptic area during slow-wave sleep led to short-latency development of desynchronization of bioelectrical activity in the neocortex and initiated the development of paradoxical sleep or a similar state. Stimulation of this structure during paradoxical sleep led to a decrease in its duration, to the virtually complete disappearance of the tonic stage of paradoxical sleep, and to an increase in the frequency of rapid eye movements in the phasic stage. Rearrangement of neuron activity in the medial preoptic area during the sleep-waking cycle was similar to that seen in cells of the lower brainstem "executive" centers of paradoxical sleep. It is suggested that neurons in the medial preoptic area of the hypothalamus are actively involved in the mechanisms of paradoxical sleep and, in particular, in the desynchronization of neocortical bioelectrical activity which develops during this stage.

Dynamics of neuron activity in the lateral preoptic area of the hypothalamus during the sleep-waking cycle.

Chronic experiments were performed on cats to study neuron spike activity in the lateral preoptic region of the hypothalamus in active and calm arousal and in the slow-wave and paradoxical phases of sleep. The dynamics of spike frequencies and the patterns of activity in the sleep-waking cycle allowed neurons to be divided into three populations. Cells showing increases in the frequency of single spikes as the level of consciousness decreased, on the transition to slow-wave sleep and then to the paradoxical phase of sleep were assigned to the "anti-waking" system, which, being a component of the somnogenic system of the brain, is involved in the mechanisms initiating and increasing the depth of sleep by inactivating the arousal-maintaining system. Cells with maximum spike frequencies in light, slow-wave sleep and demonstrating single and train discharges in association with "sleep" spindles, were regarded as elements of the system responsible for forming this state. The remaining neurons had activity characteristics which were similar in the active arousal state and paradoxical sleep and decreased their spike frequencies in calm arousal and the slow-wave phase of sleep in parallel with the transition from the continuous-arithmetic to the mixed type of activity. Changes in the activity of this type of cell during the sleep-waking cycle appear to reflect rearrangements in controlling influences from the somnogenic and arousal systems of the brain.

Role of the Lateral Preoptic Area in Sleep-Related Erectile Mechanisms and Sleep Generation in the Rat

Penile erections are a characteristic phenomenon of paradoxical sleep (PS), or rapid eye movement sleep. Although the neural mechanisms of PS-related erections are unknown, the forebrain likely plays a critical role (Schmidt et al., 1999). The preoptic area is implicated in both sleep generation and copulatory mechanisms, suggesting it may be a primary candidate in PS erectile control. Continuous recordings of penile erections, body temperature, and sleep-wake states were performed before and up to 3 weeks after ibotenic acid lesions of the preoptic forebrain in three groups of rats. Neurotoxic lesions involving the medial preoptic area (MPOA) and anterior hypothalamus (n = 5) had no significant effects on either erectile activity or sleep-wake architecture. In contrast, bilateral lesions of the lateral preoptic region, with (n = 4) or without (n = 5) MPOA involvement, resulted in a significant decrease in the number of erections per hour of PS, number of PS-related erections, and PS phases exhibiting an erection. Lesion analysis revealed that the candidate structures for PS erectile control include both the lateral preoptic area (LPOA) and ventral division of the bed nucleus of the stria terminalis; however, lesions of the LPOA were the most effective in disrupting PS erectile activity. LPOA lesioning also resulted in a long-lasting insomnia, characterized by the significant increase in wakefulness and decrease in slow wave sleep (SWS). PS architecture and waking-state erections remained unchanged after lesion in all groups. These data identify an essential role of the LPOA in both PS-related erectile mechanisms and SWS generation. Moreover, higher erectile mechanisms appear to be context-specific because LPOA lesioning selectively disrupted PS-related erections while leaving waking-state erections intact.

The effects of spinal or mesencephalic transections on sleep-related erections and ex-copula penile reflexes in the rat.

The neural mechanisms of penile erections during paradoxical sleep (PS) remain unknown since it has yet to be the subject of neurophysiological investigation. Using a new experimental model for sleep-related erection research in freely behaving rats, neural transections were undertaken to definitively elucidate the effects of paraplegia on PS-related erections and to determine at which brain level the mechanisms underlying PS erectile activity are generated. Continuous polygraphic recordings, as well as ex-copula penile reflexes, were performed in male Sprague Dawley rats before and after spinal (n = 4) or mesencephalic (n = 6) transections. Spinal transections virtually eliminated PS-related erections. Following mesencephalic transections, PS remained qualitatively intact in all rats. PS erectile activity, however, was severely disrupted, as shown by a significant decrease in the total number of erections, the number of erections per hour, and the percentage of PS phases exhibiting an erectile event. Finally, spinal and mesencephalic transections had contrasting effects on ex-copula penile reflexes. Spinal transections significantly shortened the latency to reflex induction and increased the percentage of tests eliciting an erectile event, whereas mesencephalic transections significantly increased the latency to reflex induction without affecting the percentage of tests eliciting an erectile event. These data suggest that the brainstem is not sufficient for the generation of PS erectile activity even though it is sufficient for the generation of other classic PS phenomena. We conclude that neural structures rostral to the mesencephalopn (i.e., the forebrain) are essential for the maintenance and integrity of PS related-erections. The reflex erection data suggest that spinal transection removes a tonic descending inhibition of erections, whereas such an inhibition not only remains intact, but appears enhanced following mesencephalic transection. We hypothesize that the forebrain plays a facilitatory role in erectile control, at least in part, through disinhibition of brainstem tonic anti-erectile mechanisms.

Effect of emotional stressing on organization of the waking-sleep cycle in rats of different ages

In chronic experiments on 27 late, postnatal, pubertate, and adult rats, organization of the waking-sleep cycle was studied after long-lasting emotional stressing. The pattern of disturbances in the limbico-neocortical mechanisms, responsible for organization of the above cycle, is shown to be age-dependent. In late postnatal and pubertate rats, stressing decreased the duration of the waking phase and prolonged the stage of slow-wave deep sleep. In adult rats, the waking phase became longer, while the stage of deep slow-wave sleep was stabilized Changes in the paradoxical sleep phase were insignificant.

Firing of inferior colliculus neurons in response to low-frequency sound stimulation during sleep and waking.

In vivo extracellular recordings of 102 units in the central nucleus of the inferior colliculus (IC), were made in chronically implanted guinea-pigs during the sleep/wake cycle. During wakefulness, the units were classified according to their response characteristics. Most neurons (63%) recorded showed changes, increasing or decreasing in the number of evoked discharges during the animal's transitions between wakefulness and slow-wave sleep. In the paradoxical sleep phase, the result was similar; changes were observed in most neurons, while only 11% of units did not shift their discharge pattern during ipsilateral sound stimulation. The post-stimulus time histogram of the overall evoked pattern of discharge showed sleep/wake dependency, i.e. changed in 35% of the units recorded during the 50 ms of sound stimulation. Fifty-five percent of auditory neurons did not show any change in the spontaneous firing rate during slow-wave sleep as compared to the previous waking period, while 22% exhibited a discharge increase and 23% decreased their firing. During paradoxical sleep, 14 out of 17 cells increased their spontaneous firing rate. The IC auditory neurons send descending connections to regions such as the dorsal pontine nuclei, known to mediate sleep processes. Thus, for constant auditory input, the firing rate or number of discharge variations are due to functional shifts in the sleeping brain. Auditory processing is present during sleep and differs from that observed during wakefulness. Differences were observed in the evoked firing number and/or spontaneous rate, as well as in the pattern of discharge. The ultimate reason for auditory unit shifts during sleep remains yet unexplained.

An investigation of hippocampal theta rhythm of rats as a nonlinear dynamic process.

The results of an investigation of the hippocampal theta rhythm of rats in the paradoxical phase of sleep and during orienting behavior by the method of estimation of attractor dimension are presented in this article. It has been demonstrated that the hippocampal theta rhythm consists of a regular constituent and an irregular constituent of high dimension, the interrelationship of which varies within wide limits depending upon the state of the animal. Frequency components of the regular and irregular constituents were identified. The mechanisms of their formation are considered and some hypotheses regarding their biological nature are proposed.

Hippocampal theta activity following selective lesion of the septal cholinergic systeM

The characteristic electroencephalographic patterns within the hippocampus are theta and sharp waves. Septal neurons are believed to play an essential role in the rhythm generation of the theta pattern. The present study examined the physiological consequences of complete and selective damage of septohippocampal cholinergic neurons on hippocampal theta activity in rats. A selective immunotoxin against nerve growth factor receptor bearing cholinergic neurons (192 immunoglobulin G-saporin), [Wiley R.G. et al. (1991) Brain Res. 562, 149–153] was infused into the medial septal area (0.11–0.42 μg). Hippocampal electrical activity was monitored during trained wheel running, drinking and the paradoxical phase of sleep, as well as following cholinomimetic treatment. A moderate dose of toxin (0.21 μg) eliminated the septohippocampal cholinergic projection, as evidenced by a near total absence of choline acetyltransferase-immunoreactive neurons in the medial septum and the vertical limb of the diagonal band, and by the absence of acetylcholinesterase-positive fibers in the dorsal hippocampus. In the same rats, parvalbumin immunoreactivity, a reliable marker for septohippocampal GABAergic neurons, [Freund T.F. (1989) Brain Res. 478, 375–381], remained unaltered. In addition, retrograde transport of the tracer fluorogold demonstrated that the parvalbumin cell population preserved its axonal projection to the hippocampus. Following toxin treatment, the power of hippocampal theta, but not its frequency, decreased in a dose-dependent manner. Reduction of theta power occurred between three and seven days after the toxin treatment and remained unaltered thereafter up to eight weeks. A dose which eliminated all septohippocampal cholinergic neurons (0.21 μg) left a small but significant theta peak in the power spectra during wheel running, paradoxical phase of sleep and intraseptal infusion of carbachol (5μg). Peripheral administration of physostigmine (1 mg/kg) induced only slow (1.5–2.0 Hz) rhythmic waves. No changes were observed in the gamma (50–100 Hz) band. These findings indicate that the integrity of the septohippocampal GABAergic projection is sufficient to maintain some hippocampal theta activity. We hypothesize that cholinergic neurons serve to increase the population phase-locking of septal cells and thereby regulate the magnitude of hippocampal theta.

Effect of deprivation of the paradoxical phase of sleep on activity of opiate receptors isolated from rat brain synaptic membranes

Effect of deprivation of the paradoxical phase of sleep on activity of opiate receptors isolated from rat brain synaptic membranes

Study of the 5-HT 2 antagonist ritanserin on sleep-waking cycle in the rat

Ritanserin, a 5-HT 2 receptor antagonist, was injected intraperitoneally to rats at light onset. It was found that 0.63 mg/kg decreased waking, increased the slow waves characteristic of the first stage of sleep, and decreased paradoxical sleep (PS) during the first four hours. Active waking was further decreased and slow wave stage increased during the following four hours. The number of synchronized and paradoxical sleep phases decreased whereas their duration increased during the first four hours. Ritanserin at 2.5 mg/kg decreased active waking and PS, whereas quiet waking and slow wave stage were increased during the first four hours. Quiet waking was increased during the following four hours. It is concluded that serotonin acting on 5 HT 2 receptors is actively involved in sleep-waking regulation.

Evocation in paradoxical sleep of a hippocampal conditioned cellular response acquired during waking

This experiment was a test of the possibility that a conditioned hippocampal response acquired during wakefulness could be evoked during paradoxical sleep (PS). After one session of habituation to a tone, waking rats underwent conditioning in four sessions during which the tone was used as the conditioned stimulus preceding a footshock. Pseudoconditioned animals received unpaired tone-shock presentations. There was a 24-h intersession interval. After each session, the same tone, never awakening the animal, was presented during PS phases. Hippocampal multiunit activity (MUA) was analyzed at each tone presentation during waking and during PS. Before conditioning, tone presentation did not affect MUA. During conditioning sessions, it elicited sustained increases in hippocampal discharge. When the tone was presented during postlearning PS, it induced a short-lasting increase in MUA. On the other hand, in the pseudoconditioned animals, hippocampal activity failed to show any change in response to the tone, whether during wakefulness or during PS. These results suggest that a behaviorally significant stimulus can be recognized during PS.

Effect of deprivation of the paradoxical phase of sleep on rotational and stereotyped behavior induced by selective agonists of dopamine receptors

Effect of deprivation of the paradoxical phase of sleep on rotational and stereotyped behavior induced by selective agonists of dopamine receptors