The promnesic neurosteroid pregnenolone sulfate increases paradoxical sleep in rats

The effect of systemic administration of the neurosteroid pregnenolone sulfate (PREG-S) on sleep-wakefulness cycle and on spatial memory performances was investigated in male Sprague-Dawley rats. In the first experiment, the effect of PREG-S administration (saline, 4.75, 47.5 mg/kg, i.p.) on 24 h EEG recording was evaluated. In the second experiment, spatial memory performance in a two-trial memory task was evaluated after post-acquisition administration of similar doses of PREG-S as in the first experiment. Results show that PREG-S increases paradoxical sleep and improves the performance on the memory task yielding similar dose response curves. Starting 4 h after administration of 47.5 mg/kg PREG-S, paradoxical sleep is increased for 10 h. The PREG-S effect on spatial memory lasts for at least 24 h after injection. These results suggest that an enhancement of paradoxical sleep may be involved in the promnesic effects of this neurosteroid.     

Cholinergic modulation of inhibitory avoidance impairment induced by paradoxical sleep deprivation

1. Male Wistar rats were submitted to paradoxical sleep deprivation for 96 hr by a modified multiple platform technique. 2. Training of step-through inhibitory avoidance was performed immediately after the last day of paradoxical sleep deprivation. Twenty-four hr after training the animals were submitted to the retention test. 3. In Experiment 1, pilocarpine (4 mg/kg, i.p.) or atropine (4 mg/kg, i.p.) were administered daily during the paradoxical sleep deprivation period. Pilocarpine, but not atropine, reversed the impairment induced by PS deprivation. 4. In Experiment 2, pilocarpine (4, 8 and 12 mg/kg, i.p.) was injected 1 hr before training in order to verify if the reversal of memory impairment was an effect secondary to residual enhanced blood levels of pilocarpine during training. Acute treatment with pilocarpine, in any dose, did not reverse the impairment produced by paradoxical sleep deprivation 5. Activation of the cholinergic system during the period of deprivation is able to prevent memory deficits induced by paradoxical sleep deprivation.     

Effects of aging and D-glucose on locomotor activity, spontaneous alternation, and plasma glucose levels in preweanling Sprague-Dawley rats

Previous research has shown that developmentally related memory impairments in immature rodents are malleable and may be attenuated using a variety of pharmacological and behavioral treatments. This experiment examined the effects of glucose (10, 100, 250 or 500 mg/kg) or saline on blood glucose level, locomotor activity, and spontaneous alternation (SA) in the T-maze. Studies were conducted with 20-, 22-, and 24-day-old preweanling Sprague-Dawley rats. Results indicated a general decline in blood glucose level with age and size of glucose injection. The largest overall decline in blood glucose was found following the 500 mg/kg dose in 24-day-old animals. An increase in T-maze arm entries with age indicated increased exploratory activity. SA generally improved with age, but glucose had no reliable effect on behavior. The ontogenetic state of the nervous system, including changes in cholinergic system activity, glucoregulation, and proliferation of glucose transporters, is discussed.     

Amygdala kindling effects on sleep and memory in rats

Sleep disturbances accompany the development of amygdaloid-kindled seizures in cats. Some of these sleep deficits resemble those seen in aged rats; these latter changes in sleep patterns are correlated with memory impairments in the aged animals. In the present study, we examined the hypothesis that sleep deficits after kindling may be related to memory impairments. Rats were kindled for 4 weeks (2-2.5 weeks after stage 5 seizures) and were then allowed a one week recovery period. Sleep patterns were assessed through-out the kindling and recovery periods. The animals were then trained on an inhibitory avoidance apparatus and tested for retention 24 h later. Only transient sleep changes occurred during the development of kindling (to stage 5 seizures). However, continued kindling resulted in significant reductions in several sleep measures which remained depressed for at least one week after the termination of the kindling trials. As a group, kindled rats were impaired in retention of the inhibitory avoidance learned response. In kindled animals, retention performance was significantly correlated with total paradoxical sleep, the ratio of paradoxical/total sleep, and paradoxical sleep, the ratio of paradoxical/total sleep, and paradoxical sleep bout duration. These correlations are consistent with the view that deficits in paradoxical sleep may be related to deficits in some forms of memory.     

Effects of 3-nitropropionic acid administration on memory and hippocampal lipid peroxidation in sleep-deprived mice

Numerous studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the effects of a pro-oxidant agent--3-nitropropionic acid (3-NP)--on hippocampal oxidative stress and passive avoidance performance of sleep-deprived mice. Mice were repeatedly treated i.p. with saline or 5 or 15 mg/kg 3-NP and sleep-deprived for 24 h by the multiple platform method--groups of 4-5 animals placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface or kept in their home cage (control groups). The results showed that: (1) neither a 24 h sleep deprivation period nor 3-NP repeated treatment alone were able to induce memory deficits and increased hippocampal lipid peroxidation; (2) this same protocol of sleep deprivation, combined with 15 mg/kg 3-NP repeated treatment, induced memory deficits and an increase in hippocampal lipid peroxidation. The results support the involvement of hippocampal oxidative stress in the memory deficits induced by sleep deprivation and the hypothesis that normal sleep would prevent oxidative stress.     

Selegiline protects against recognition memory impairment induced by neonatal iron treatment

Excess of iron in the brain has been implicated in the pathogenesis of several human neurodegenerative diseases, for example Alzheimer's disease and Parkinson's disease. It has been shown that the neonatal period is critical for the establishment of normal iron content in the adult brain. Moreover, it is known that aging alters the cerebral distribution of this metal. We have recently described that neonatal administration of iron severely impaired novel object recognition memory in rats. The aim of the present study was to determine whether selegiline, a monoamine oxidase (MAO) inhibitor known for its neuroprotective properties, could protect rats against cognitive impairment induced by neonatal administration of iron. In the first experiment, male Wistar rats received vehicle (5% sorbitol in water) or iron (10.0 mg/kg) orally from postnatal days 12 to 14 and saline (0.9% NaCl) or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting 24 h before the first iron dosing. In the second experiment, rats were given either vehicle or iron (10.0 mg/kg) orally from postnatal days 12 to 14 followed by saline or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting when rats reached adulthood (50th day after birth). Iron-treated rats given selegiline in both doses showed no deficits in recognition memory. Rats receiving iron but no selegiline presented memory deficits. This is the first study reporting the reversion of iron-induced memory impairment, supporting the view that our model can be considered as a useful tool in the search for new drugs with neuroprotective and/or memory enhancing properties.     

Involvement of dopamine receptors in cocaine-induced genital reflexes after paradoxical sleep deprivation

Previous work has demonstrated that paradoxical sleep deprivation (PSD) potentiates cocaine-induced genital reflexes in male rats. To examine the possibility that this effect might involve alterations in binding to the DA transporter (DAT), we examined [3H] WIN 35,248 binding in brain after 96 h of PSD. No changes were found in any of the 11 brain regions examined. Since we had previously identified changes in D2 receptor binding after PSD, we next examined the effects of DA receptor subtype antagonists on cocaine-induced reflexes in sleep-deprived rats. Separate groups of PSD rats received saline, haloperidol (0.4, 0.8 or 1.6 mg/kg), SCH 23390 (0.25, 0.5, 1 mg/kg) or sulpiride (50, 100, 200 mg/kg) 60 min prior to acute cocaine (7 mg/kg). In saline pretreated rats, cocaine-induced penile erection (PE) in 100% of SD rats. This percentage was not significantly reduced by haloperidol at any dose, but was significantly reduced in rats pretreated with SCH 23390 (1 mg/kg) or sulpiride (100 or 200 mg/kg). In addition, acute cocaine-induced ejaculation in 80% of SD rats. This effect was not affected by haloperidol at any dose, but was significantly reduced by all doses of SCH 23390 and by the 200 mg/kg dose of sulpiride. These results suggest that the potentiating effects of cocaine on penile erection and ejaculation are likely due to PSD-induced changes in DA postsynaptic receptor sensitivity rather than alterations in DA transporter. They further suggest that both D1 and D2 receptors may play a role in these effects.     

Sleep and Epilepsy: A Key Role for Nitric Oxide?

PURPOSE: It has been suggested that nitric oxide (NO) is involved in sleep mechanisms and in the pathophysiology of epilepsy. Data are, however, controversial because it is not clear whether NO facilitates sleep or waking, or whether it exerts pro-or antiepileptic influences. METHODS: The question was considered through NO voltammetric measurements and electroencephalographic recordings performed in GAERS rats (Genetic Absence Epilepsy Rat from Strasbourg): an experimental model of "petit-mal" human disease. Regulatory processes of sleep and epilepsy were studied after administration of a NO synthase inhibitor [l-arginine-p-nitroanilide (l-ANA) 100 mg/kg i.p.], a NO donor (SIN-1 100 ng/2 microl i.c.v.), and the antiepileptic drugs used in clinic [valproate (VPA 200 mg/kg i.p.) and ethosuximide (ESM 100 mg/kg i.p.)]. RESULTS: In GAERS rats, spontaneous circadian organizations of spike-wave discharges and paradoxical sleep (PS) occur in an opposite way; spontaneous NO concentrations are higher during seizures than during wakefulness, slow-wave sleep, and PS, respectively. l-ANA induces a disappearance of NO peak, an epileptic induction, and a loss of PS while SIN-1 induces opposite effects. Antiepileptic effects of VPA and ESM are associated with a PS increase and a significant release of NO. CONCLUSIONS: These results indicate that NO could be, in GAERS rats, a central piece in the reciprocal inhibitory mechanisms regulating the induction of PS and spike-wave discharges. NO could prevent absence epilepsy and act as an antiepileptic substance in facilitating PS. Antiepileptic efficiency of VPA and ESM may work through their ability to release NO. A track for a new treatment of petit-mal disease in children can be envisioned.     

Sensitivity to cholinergic drug treatments of aged rats with variable degrees of spatial memory impairment

As a first step, the present experiment aimed at characterizing learning and memory capabilities, as well as some motor and sensorimotor faculties, in aged (24-26.5 months) Long-Evans female rats. As a second step, a psychopharmacological approach was undertaken in order to examine the sensitivity of aged rats to muscarinic blockade and to cholinomimetic treatments. Young adult (3-5.5 months) and aged rats were tested for beam-walking performance, locomotor activity in the home cage and an open field, and spatial learning/memory performance in a water maze and a radial maze. Spontaneous alternation rates were assessed in a T-maze. Statistical analysis discriminated between aged rats showing moderate impairment (AMI) and those showing severe impairment (ASI) in the water maze test. Beside their different degrees of impairment in the water maze, AMI and ASI rats were similarly (no significant difference) impaired in beam-walking capabilities, home cage activity and radial maze performance. In the spontaneous alternation task aged rats were not impaired and, in the open-field test, AMI rats were hypoactive, but not as much as ASI rats. Neither of the cognitive deficits was correlated with a locomotor or a sensorimotor variable, or with the body weight. When tested in the radial maze, a low dose of scopolamine (0.1 mg/kg i.p.) produced memory impairments which were significant in AMI and ASI rats, but not in young rats. Combined injections of scopolamine and physostigmine (0.05 and 0.1 mg/kg) or tacrine (THA, 3 mg/kg) showed physostigmine (0.1 mg/kg) to compensate for the scopolamine-induced impairments only in AMI rats. whereas THA was efficient in both AMI and ASI rats. The results indicate: (i) that rats with different degrees of spatial memory impairment in the water maze are similarly hypersensitive to muscarinic blockade when tested in a radial maze test; and (ii) that under the influence of a dose of scopolamine which is subamnesic in young rats, aged rats respond to anticholinesterase treatments according to the level of performance achieved in the water maze: moderately impaired rats are sensitive to both physostigmine and THA, whereas more severely impaired rats are sensitive only to THA.     

Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle

In the present study, cortical extracellular levels of glucose were monitored for the first time throughout the sleep-wake states of the freely moving rat. For this purpose, polygraphic recordings (electroencephalogram of the fronto-occipital cortices and electromyogram of the neck muscles) were achieved in combination with differential normal pulse voltammetry (DNPV) using a specific glucose sensor. Data obtained reveal that the basal extracellular glucose concentration in the conscious rat is 0.59 +/- 0.3 m M while under chloral hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal concentration. Regarding the sleep-wake cycle, the existence of spontaneous significant variations in the mean glucose level during slow-wave sleep (SWS = +13%) and paradoxical sleep (PS = -11%) compared with the waking state (100%) is also reported. It is to be noticed that during long periods of active waking, glucose level tends towards a decrease that becomes significant after 15 min (active waking = -32%). On the contrary, during long episodes of slow-wave sleep, it tends towards an increase which becomes significant after 12 min (SWS = +28%). It is suggested that voltammetric techniques using enzymatic biosensors are useful tools allowing direct glucose measurements in the freely moving animal. On the whole, paradoxical sleep is pointed out as a state highly dependent on the availability of energy and slow-wave sleep as a period of energy saving.     

Cycloheximide impairs and enhances memory depending on dose and footshock intensity

This experiment examined the effects on memory of interactions of cycloheximide dose and training foot shock intensity. Mice received injections of cycloheximide (120 mg/kg, s.c.) or saline 30 min prior to inhibitory avoidance training with shock intensities of 100, 150, 250 or 300 μA (1 s duration). Memory was tested 48 h later. The saline control mice showed increasing memory latencies as a function of shock intensity. The ability of cycloheximide to impair memory increased as the training shock intensity increased. In a second experiment, mice were trained with a 200 μA (1 s duration) shock and received injections of saline or cycloheximide at one of several doses (30, 60 or 120 mg/kg). Under these training conditions, cycloheximide enhanced memory in an inverted-U dose-response manner. These findings are consistent with prior findings suggesting that protein synthesis inhibitors act on memory by altering modulators of memory formation as a secondary consequence of the inhibition of protein synthesis rather than by interfering with training-initiated synthesis of proteins required for memory formation.     

Differential effects of low and high doses of topiramate on consolidation and retrieval of novel object recognition memory in rats

Topiramate is a new antiepileptic drug proposed to facilitate synaptic inhibition and block excitatory receptors. However, little is known about the effects of topiramate on memory. In the first experiment, intraperitoneal injection of topiramate at doses of 10.0 and 100.0 mg/kg, immediately after training, induced a deficit in short-term memory (STM) of a novel object recognition (NOR) task tested 1.5 hours after training in rats. In a long-term memory (LTM) test given to the same rats 24 hours after training, topiramate 0.1mg/kg enhanced, whereas 10.0 and 100.0 mg/kg impaired, NOR retention. In the second experiment, administration of topiramate 0.01 and 0.10 mg/kg 1 hour prior to the LTM retention test improved NOR retention, whereas 10.0 and 100.0 mg/kg produced retrieval deficits. The results indicate that low doses of topiramate improve, whereas high doses impair, consolidation and retrieval of recognition memory in rats.     

Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice.

The involvement of 5-HT1B receptors in the regulation of vigilance states was assessed by investigating the spontaneous sleep-waking cycles and the effects of 5-HT receptor ligands on sleep in knock-out (5-HT1B-/-) mice that do not express this receptor type. Both 5-HT1B-/- and wild-type 129/Sv mice exhibited a clear-cut diurnal sleep-wakefulness rhythm, but knock-out animals were characterized by higher amounts of paradoxical sleep and lower amounts of slow-wave sleep during the light phase and by a lack of paradoxical sleep rebound after deprivation. In wild-type mice, the 5-HT1B agonists CP 94253 (1-10 mg/kg, i.p.) and RU 24969 (0.25-2.0 mg/kg, i.p.) induced a dose-dependent reduction of paradoxical sleep during the 2-6 hr after injection, whereas the 5-HT1B/1D antagonist GR 127935 (0.1-1.0 mg/kg, i.p.) enhanced paradoxical sleep. In addition, pretreatment with GR 127935, but not with the 5-HT1A antagonist WAY 100635, prevented the effects of both 5-HT1B agonists. In contrast, none of the 5-HT1B receptor ligands, at the same doses as those used in wild-type mice, had any effect on sleep in 5-HT1B-/- mutants. Finally, the 5-HT1A agonist 8-OH-DPAT (0.2-1.2 mg/kg, s.c.) induced in both strains a reduction in the amount of paradoxical sleep. Altogether, these data indicate that 5-HT1B receptors participate in the regulation of paradoxical sleep in the mouse.     

Effects of elevated plasma magnesium versus calcium on cerebral ischemic injury in rats

Both Mg2+ and Ca2+ have been implicated as having roles in the pathomechanisms of cerebral ischemia. To further study the effects of these ions on postischemic histologic outcome, fasted rats were given one of three intravenous infusions: 5.0 mmol/kg MgCl2, 5.0 mmol/kg MgCl2 + 0.035 units/kg regular insulin, or 1.0 mmol/kg CaCl2. This resulted in elevated plasma Mg2+ or Ca2+ concentrations in the corresponding groups. A fourth group received 0.9% NaCl (saline). Preinfusion plasma glucose concentration was similar for all groups and was unchanged after infusion in rats receiving either saline or MgCl2 + insulin. In contrast, postinfusion glucose concentration was increased in the MgCl2 group (p less than 0.001) and decreased in the CaCl2 group (p less than 0.001) relative to saline-treated rats. Following respective infusions, all rats underwent 10 minutes of reversible forebrain ischemia (bilateral carotid artery occlusion and systemic hypotension) followed by 7 days' recovery. Six of 12 CaCl2-treated rats died 2-3 days after ischemia; all other rats remained neurologically indistinguishable, without gross neurologic deficits. Histologic injury in the neocortex and caudate was moderate in all groups. In the hippocampus, MgCl2 + insulin resulted in 66 +/- 6% (mean +/- SD) dead CA1 pyramidal cells, which was similar to the amount in saline-treated rats (68 +/- 10%). Injury was increased in the MgCl2 group (79 +/- 4% dead cells), while in surviving CaCl2-treated rats, injury was decreased (54 +/- 13%). We conclude that the increased injury in MgCl2-treated rats and the decreased injury noted in surviving rats receiving CaCl2 are due to the plasma glucose concentrations present prior to ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the blood-brain barrier in the anticholinergic differential effects on LH and prolactin release in proestrous rats

The effects of homatropine and atropine on plasma LH and prolactin (PRL) levels during the afternoon of pro-oestrus were investigated. Homatropine methylbromide was unable to block the spontaneous increase of LH but prevented the prolactin surge in pro-oestrous rats at doses of 450 and 700 mg/kg s.c. Atropine sulphate blocked both LH and PRL at doses of 450 and 700 mg/kg s.c. These two anticholinergics when injected into the 3rd ventricle (250 mug/rat) blocked the pro-oestrus increase of LH and inhibited PRL. Pharmacological experiments were performed in parallel and the injection of either homatropine or atropine (450 mg/kg s.c.) resulted in the abolishment of peripheral toxic signs induced by pilocarpine (50 mg/kg s.c.) whereas its central toxic signs were prevented by atropine but not by homatropine. Our findings suggest that the difference in action of systemic injections of atropine and homatropine on LH and PRL release is explained by a relatively low permeability of homatropine to the brain. Therefore, cholinergic LH-controlling mechanisms may be situated above the median eminence and those related to PRL placed outside the blood-brain barrier.     

Influence of paradoxical sleep deprivation and cocaine on development of spontaneous penile reflexes in rats of different ages

Recent studies have established that paradoxical sleep deprivation (PSD) and cocaine administration induce genital reflexes (penile erection and ejaculation) in adult and old rats. To determine whether the same effects would induce spontaneous genital reflexes in rats of different ages (30-90 days old), we administered with cocaine (7 mg/kg) or saline to rats after a 4-day period of PSD, or at the equivalent time-point in control animals, and penile erection and ejaculation were then evaluated. In PSD rats administered cocaine, erection was observed from 30 days old to 90 days old, when both genital reflexes reached a peak. Animals submitted to PSD and saline injection showed erection from 60 to 90 days old. None of the control (saline and cocaine) groups of any age displayed these behaviors. The effects of PSD on steroid hormone levels showed that, although testosterone levels increased with age, PSD caused a marked decrease in testosterone at all ages evaluated. Progesterone and corticosterone levels were higher in PSD groups than in the respective control groups. These findings suggest that the interaction of PSD and cocaine probably enhances dopaminergic transmission in the brain and may accelerate the development of genital reflexes in male rats.     

Paradoxical sleep deprivation modulates tyrosine hydroxylase expression in the nigrostriatal pathway and attenuates motor deficits induced by dopaminergic depletion

The nigrostriatal pathway is very likely involved in sleep regulation, considering the occurrence and high prevalence of sleep-related disorders in patients with Parkinson's disease. Indeed, dopaminergic neurons in the ventral tegmental area were recently shown to fire in bursts during paradoxical sleep (PS), but little is known about the activity of the nigrostriatal dopamine (DA) cells in relation to PS. In view of that we hypothesized that paradoxical sleep deprivation (PSD) may play a relevant role in nigrostriatal tyrosine hydroxylase (TH) expression and, subsequently, in sleep rebound. The present study was designed to determine the effects of PSD in the nigrostriatal pathway in mice by means of neurochemical and behavioral approaches. Intraperitoneal reserpine (1 mg/kg) associated to α-methyl-p-tyrosine (αMT) (250 mg/kg) to produce catecholamine depletion, or rotenone (10 mg/kg) to increase striatal DA turnover were injected 30 min before the 24 h of PSD. Catalepsy and open-field tests indicated that motor deficits induced by reserpine-αMT were counteracted by PSD, which, in contrast, potentiated the motor impairment induced by rotenone. Besides, PSD produced down-regulation on TH expression within the substantia nigra pars compacta and striatum, without affecting the number or the optical density of dopaminergic neurons present in the respective areas. Interestingly, PSD potentiated the downregulation of TH expression in the substantia nigra pars compacta and striatum induced by the co-administration of reserpine-αMT. These results reinforce the notion of a strong participation of DA in PS, as a consequence of the modulation of TH protein expression in the nigrostriatal pathway.     

The evaluation of antimuscarinic-induced convulsions in fasted rats after food intake

The present study was performed to evaluate convulsions after food intake in fasted rats pretreated with scopolamine or atropine and to determine whether these convulsions respond to drugs found effective in fasted mice. Scopolamine (2.4 mg/kg) and atropine (2.4 mg/kg) were given intraperitoneally (i.p.) to rats fasted for 52h. Both drugs induced convulsions after animals were allowed to eat ad lib. Another group of fasted rats pretreated with saline, MK-801 (0.1mg/kg), clonidine (0.1mg/kg), chlorpromazine (2 and 4 mg/kg), valproate (200mg/kg), diazepam (1.5 and 2mg/kg) or gabapentin (50mg/kg) were treated i.p. with saline or scopolamine (2.4 mg/kg) and were allowed to eat ad lib. Clonidine, MK-801, chlorpromazine (4 mg/kg) and diazepam (2 mg/kg) reduced the incidence of scopolamine-induced convulsions in fasted rats. Gabapentin could only prolong the onset of convulsions. Neither treatment was effective against myoclonus of hindlimbs. Present results showed that fasted rats also develop antimuscarinic-induced convulsions which do not completely respond to treatments found effective in convulsions of fasted mice.     

Atropine-sensitive and -insensitive components of the somatosensory evoked potential

The evoked potential in primary somatosensory cortex changes with time. Short puffs of air administered to the nose of awake, quietly resting adult rats elicited potentials that could be altered by one of several treatments (saline, atropine methyl nitrate or atropine sulfate). The change produced by blocking muscarinic receptors in the central nervous system with atropine sulfate (100 mg/kg) was the largest, but control substances also altered the potential, suggesting that the gradual changes observed in the evoked potential 30 min after intraperitoneal injection may also be affected by factors such as the stress associated with injection itself and the blockade of peripheral muscarinic receptors. The changes observed in the evoked potential when central cholinergic receptors are blocked include a large shift towards positivity in the early components (between 18 and 64 ms with maxima at 20 and 47 ms) and a similarly significant shift towards negativity in the later components (between 90 and 208 ms with maxima at 115 and 157 ms). The actual changes observed during inactivation of central muscarinic receptors suggest that the role of acetylcholine during arousal is more than to simply bias the cortex towards greater excitability. Rather, the muscarinic receptors on inhibitory interneurons or on the dendritic terminals of pyramidal cells in superficial layers of cortex enhance the first intracortical synaptic events but reduce the population response at later times during the first 250 ms following a tactile stimulus.     

Progressive paradoxical sleep deprivation impairs partial memory following learning tasks in rats*★

BACKGROUND： Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by ＂flower pot＂ technique, on spatial reference memory and working memory require further research. OBJECTIVE： To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING： Controlled observation experiment. The experiment was performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from December 2006 to October 2007. MATERIALS： Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS： All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the ＂flower pot＂ technique for 72 hours, housing the rats on small platforms over water. Rats in the ＂tank control＂ and ＂home cage control＂ groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES： Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems for Morris Water Ma