Reduction in paradoxical sleep after L-dopa administration in rats

The EEG and EMG activity of two groups of rats (N = 8 each) was recorded during one experimental and 5 control days. On the experimental day, one group received 125.0 mg/kg L-dopa preceded by 50.0 mg/kg benserazide hydrochloride. The other group received 1.0 mg/kg haloperidol, immediately before the recording session. After L-dopa plus benserazide administration the total time and the number of episodes of paradoxical sleep and slow wave sleep decreased significantly compared to control sessions.     

Effects of different substance misuse in genital reflexes of paradoxical sleep deprived male rats

As psychostimulants are widely abused, their neurochemical and behavioral effects have been extensively studied for many years. Our previous data demonstrate that paradoxical sleep deprivation (PSD) enhances drug-induced penile erection and ejaculation. PSD in association to drugs of abuse like cocaine potentiated genital reflexes in male rats. In this sense, the present study investigated if three substances abused by young people--such as Delta(9)-tetrahydrocannabinol (Delta(9)THC), alcohol and caffeine--had any significant effect on the genital reflexes in PSD rats. The results indicated that PSD induced erection in 50% of the rats and 20% ejaculated. In addition, there was no significant alteration in the number of animals exhibiting genital reflexes neither on the frequency of these behaviors when challenged with Delta(9)-THC or alcohol or caffeine after 96 h of PSD. These findings show that Delta(9)THC, alcohol and caffeine when administrated isolated did not produce alterations in genital reflexes in the PSD male rats.     

Glucose treatment reduces memory deficits in young adult rats fed high-fat diets

Feeding rats high-fat diets for 3 months produces a widespread cognitive deficit that affects performance on a wide range of learning and memory tasks. The present study tested the hypothesis that this effect is related to a fat-induced impairment in glucose metabolism. Following 3 months of dietary intervention (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow), male Long-Evans rats were tested on a variable interval delayed alternation (VIDA) task that measures learning and memory functions that differentially involve specific brain regions. Relative to rats fed chow, rats consuming the high-fat diets were impaired on all aspects of VIDA performance. Following baseline testing, rats were maintained on their respective diets and the effect of glucose administration (100 mg/kg BW; i.p.) was examined. For the next 6 days, animals alternately received injections of saline or glucose 30 min prior to VIDA testing. Glucose treatment improved performance, with the effect being most pronounced at the longer intertrial intervals where task performance is sensitive to hippocampal impairment. Importantly, the beneficial effect of glucose were confined to those animals consuming the high-fat diets and were not observed in rats fed chow. These results demonstrate that glucose administration can overcome those deficits associated with hippocampal function in rats fed high-fat diets and are consistent with the hypothesis that high-fat diets, in part, mediate their effect through the development of insulin resistance and glucose intolerance.     

Neuroleptic-induced attenuation of brain stimulation reward in rats.

In 30-min free-operant tests, the dopamine receptor blockers pimozide (.125, .25, and .50 mg/kg) and (+)-butaclamol (.1, .2, and .4 mg/kg) attenuated lever pressing for lateral hypothalamic brain stimulation. When discrete self-stimulation trials were offered in a straight alleyway, pimozide increased start box latencies, slowed running speeds, and reduced lever-pressing rates. However, performance early in both lever-pressing and runway sessions was normal; performance deteriorated as testing progressed, following patterns that paralleled those seen when animals were tested with reductions in the amplitude of stimulating current. Spontaneous recovery was obtained in both situations; experimenter-imposed 10-min time-outs caused renewed lever pressing and running. In contrast, alpha-noradrenergic receptor blockade by phenoxybenzamine (5, 10, and 20 mg/kg) failed to produce extinction-like response patterns. These data support the view that central dopaminergic systems are important components of the neural mechanisms mediating reward.     

Avoidance performance in rat enhanced by postlearning paradoxical sleep deprivation

This series of experiments investigates possible relations between increases in paradoxical sleep (PS), persisting for several days after an avoidance training, and improvement of retention performance that occurred 3 days following partial training in a brightness discrimination Y-maze shock-avoidance task. Sprague-Dawley rats were trained in the Y-maze and PS deprived for 24 h either immediately or 24, 48, or 72 h following initial training. Contrary to what was expected, the results indicated that PSD immediately following the training session enhanced the avoidance performance after a 7-day retention interval. PSD at later times had no effect. Experiment 2 indicated that this effect was obtained only for PS-deprived animals and not for those placed in the PSD situation, but on larger platforms. Thus enhancement of the avoidance performance was not due to increases in stress or arousal caused by PSD-associated factors. Experiment 3 showed that the facilitative effect of a non-delayed 24-h PSD was obtained immediately thereafter as well as 24 h later, demonstrating that this effect was not due to any PS rebound which might have occurred following the PSD. Alternative explanations for these unexpected results are discussed.     

Glucose effects on mecamylamine-induced memory deficits and decreases in locomotor activity in mice.

Peripheral glucose administration attenuates the effects of muscarinic cholinergic antagonists on several measures, including spontaneous alternation, inhibitory avoidance, and locomotor activity. The present study examined glucose interactions with mecamylamine, a nicotinic cholinergic antagonist, on these measures. Mecamylamine (5 mg/kg, sc) significantly impaired spontaneous alternation performance. Glucose (100 mg/kg, ip) administered with mecamylamine attenuated the impairment. Treatment with hexamethonium (5 and 10 mg/kg, sc), a peripheral nicotinic blocker, did not impair performance. Pretraining treatment with mecamylamine, but not hexamethonium, significantly reduced later retention latencies on inhibitory avoidance tests. Glucose, administered with mecamylamine prior to training, significantly attenuated the impaired test performance. Mecamylamine, but not hexamethonium, significantly decreased locomotor activity. In contrast to the attenuating effects of glucose on the other measures above, glucose administered with mecamylamine potentiated the decreased locomotor activity. These findings demonstrate that glucose influences the behavioral effects of a nicotinic cholinergic antagonist in a manner generally similar to that of muscarinic cholinergic antagonists, and supports previous evidence that circulating glucose interacts with central cholinergic functions.     

Scopolamine-induced deficits in spontaneous alternation performance: attenuation with lateral ventricle injections of glucose.

This experiment determined whether centrally administered glucose can attenuate scopolamine-induced deficits in spontaneous alternation performance. All rats were surgically prepared with indwelling cannulae directed at the lateral ventricle. Thirty min prior to alternation tests, rats received systemic (ip) injections of saline or scopolamine (3 mg/kg). Ten or thirty min prior to training, the rats also received a direct injection into the lateral ventricle of either artificial cerebrospinal fluid (CSF) or glucose (3 micrograms in 1 microliter). Scopolamine significantly impaired spontaneous alternation performance relative to controls. Additional treatment with ICV glucose 30 min, but not 10 min prior to testing, significantly attenuated the scopolamine-induced deficit. These results add support to the view that glucose acts directly on brain systems to attenuate behavioral effects of cholinergic antagonists.     

Some biochemical and behavioural aspects of the paradoxical sleep window

It has recently been proposed that there is a vulnerable period of time following successful learning when paradoxical sleep (PS) is necessary for learning. This vulnerable time period has been called the PS window. In Experiment 1, the protein synthesis inhibitor anisomycin (ANI) was administered following shuttle avoidance training in the Sprauge-Dawley rat to coincide with the onset of an established PS window. Control groups received either saline or ANI either 3 hours before or 3 hours after the beginning of the PS window. Three hours after the injection, each group was retested. Then animals were immediately sacrificed, and whole brain biochemical analyses were done on levels of acetylcholine (ACh) and activity of acetylcholinesterase (AChE). Only the rats given ANI timed to coincide with the beginning of the PS window showed learning deficits. All ANI-treated groups had less ACh and AChE activity. In Experiment 2, the ACh antagonist scopolamine (SCOP) was injected at the same times as in Experiment 1, and each of these groups had a corresponding saline control group as before. Retesting was done 1 day later; once again, the only group to show learning deficits was the group receiving SCOP timed to coincide with the PS window. Results suggested that the transmitter ACh plays an important role in learning/memory processes at the PS window.     

Improvement of learning by mesencephalic reticular stimulation during postlearning paradoxical sleep

Evidences have been given which suggest that a newly formed memory trace is processed during paradoxical sleep (PS) following learning. The present experiments were aimed at testing the hypothesis that during postlearning PS the new memory trace is in a similar state as immediately after acquisition. For this purpose, a mild electrical stimulation of the mesencephalic reticular formation (MRF)--known to enhance retention performance when delivered just after learning--was administered during postlearning PS phases. Wistar rats were trained to run in a six-unit spatial discrimination maze for food reward. After each daily trial, extradural cortical electrodes (ECoG) activity was monitored polygraphically for 4 h. Half of the animals received nonawakening MRF stimulations during the first six phases of PS. Control rats received no stimulation. The learning results showed a marked improvement in performance, in terms of error number reduction, in the stimulated group. Results of a second experiment confirmed the facilitative effect of MRF stimulations given during postlearning PS. Moreover, they emphasized the specific role of PS, by showing that the same stimulations were ineffective when delivered, at the same time intervals after training, during six periods of waking or six periods of slow-wave sleep. These results lend support to the idea of a reactivation of the new memory trace during PS. They suggest that dynamic processes, similar to those immediately following acquisition or exposure to a reactivating treatment (i.e., a reminder), take place during postlearning PS.     

Possible participation of D3 and D4 dopaminergic receptors on genital reflexes induced by cocaine in paradoxical sleep deprived male rats

Previous studies have demonstrated that paradoxical sleep deprivation (PSD) potentiates cocaine-induced genital reflexes in male rats and both D1 and D2 receptors may play a role in those effects, and to examine the possibility that such might involve other dopaminergic receptors, we investigated the effects of D3 and D4 receptor subtype antagonists on cocaine-induced reflexes in sleep-deprived rats. Separate groups of PSD rats received saline, D3 (U9919A; 0.75, 1.5 and 3 mg/kg) or D4 (L745870; 0.75, 1.5 and 3 mg/kg) antagonists prior to acute cocaine challenge. Results demonstrated that U9919A induced significant reduction in the number of animals that displayed erection and the frequency of erection at two smaller doses, while no significant difference was reported for the D4 receptor antagonist. Although our studies indicate that there is a relevant participation of D3 receptors in male sexual function, D4 receptors seem not to exert an essential role in this model.     

Four hours of paradoxical sleep deprivation impairs alternation performance in a water maze in the rat

Sixteen rats were deprived of paradoxical sleep (PS) for 4 h using the "flower pot" technique and 16 other served as yoked controls. PS-deprived and control rats then had to learn a water maze using either a standard allocentric configuration (i.e., finding the submerged platform using external cues; n = 6/group) or an alternation version (goal platform alternating between two locations; n 10/group). Rats were submitted to six trials with a cutoff time of 60 s and an intertrial interval of 5 min. Criterion was set as two consecutive successful completions. PS-deprived rats made more quadrant entries and took more time to reach criterion on the alternation task than control rats while both groups were equal on the allocentric task. Based on lesion studies (Ethier et al., this issue) we propose that tasks that require an intact medial prefrontal cortex are particularly sensitive to PS deprivation.     

Glucose regulation and face recognition deficits in older adults: the role of attention

The present study investigated the perceptual, attentional, and memory processes underlying face recognition deficits observed in older adults with impaired glucoregulation. Participants were categorized as good glucoregulators or poor glucoregulators on the basis of an oral glucose tolerance test. Using event-related potential (ERP) methodology, 23 participants (62–88 years) performed a 2-stimulus oddball task. Participants were asked to rate and memorize 10 “target” faces, which were then presented amongst 120 unfamiliar foils. Behavioral results indicated that good glucoregulators were significantly more accurate at recognizing target faces. ERP markers of early visual perception (P1 and N170 components) and memory formation (P3 component) were unaffected by glucoregulatory efficiency. The P2 component, an index of attentional processing, was larger and delayed in the poor glucoregulators. To the best of our knowledge, this study is the first to suggest that face recognition deficits in poor glucoregulators may be due to impairments in attentional processing.     

Assessment of retention capacities in old rats

Young (3-6 month) and old (24-27 month) barrier reared Wistar rats were tested for their ability to retain an inhibitory (passive) avoidance, acquired immobility, and a conditioned taste aversion response as a function of time. Old rats exhibited accelerated forgetting of both the inhibitory avoidance and acquired immobility response in comparison to young rats. In contrast, old rats displayed good retention of the conditioned taste aversion response at all time intervals tested. It appears that the dynamic aspects of retention are altered in aged rats depending on the task, and in some instances may be expressed as accelerated forgetting.     

Social buffering in rats: prolactin attenuation of active interaction

Stress may result when the present environment is interpreted as threatening, and stress is known to increase the prolactin-secretory response. In the present study, rats (N=83) were exposed to a conditioned-fear paradigm (environment paired with footshock), and on testing day, rats were exposed to the experimental chamber without shock while alone (Alone n=16), with an object (Object n=17), with a euthanized conspecific (Euthanized n=16), or with a social partner (Social n=19). The control group (Control n=15) was exposed to the experimental chamber but was never shocked. The Control group had significantly lower levels of prolactin than the Alone, Object, and Euthanized groups; however, the Control group's levels of prolactin were not significantly different than that of the Social group, which was significantly lower than that for the Alone group. Social interaction decreased fear independent of the distraction provided by a stimulus in the chamber. Active touch appeared to be crucial for social buffering to occur.