John G. McCoy

Environmental enrichment: effects on spatial memory and hippocampal CREB immunoreactivity.

Environmental enrichment has been shown to improve performance in tests of spatial memory, induce neurogenesis in the hippocampus, enhance survival of newly formed granule cells, and inhibit spontaneous apoptosis. Although neuroplasticity of the mammalian brain declines with age, recent evidence suggests that the adult brain exhibits significant plasticity in response to environmental stimulation. The present study was designed to evaluate the effect of environmental enrichment on spatial memory and on immunoreactivity to cAMP response element binding protein (CREB) from the hippocampus. C57/BL/6 mice were trained in a Morris water maze after exposure to an enriched environment, either from 35 to 94 days or from 100 to 159 days of age. Hippocampal tissue from representative animals was later analyzed by Western blot for CREB immunoreactivity. Results indicate that environmental enrichment (particularly during the earlier period) improved performance on the Morris water maze and tended to increase immunoreactivity to CREB in the hippocampus. Social interaction by itself did not result in significant differences in navigational performance. Results with regard to social interaction and CREB immunoreactivity were mixed. Results are discussed in terms of evaluating the construct of enrichment, the correlation of CREB transcription and behavior change, and the importance of the developmental period for enrichment.

The cognitive cost of sleep lost.

A substantial body of literature supports the intuitive notion that a good nights sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances.

Ginkgo biloba extract: cognitive enhancer or antistress buffer.

Constituents extracted from the leaves of the Ginkgo biloba tree possess beneficial properties that may buffer the aging nervous system from deterioration due to oxidative stress. In the present investigation, a standardized extract of G. biloba (EGb 761) or an equal volume of the vehicle was administered (100 mg/kg/day) to senescent (20-month) C57BL/6 male mice for up to 82 consecutive days. Animals were tested twice in the Morris water maze (MWM) after 28 and 70 days of treatment. No differences were observed in acquisition or retention of performance on the water maze. Elevated-plus maze (EPM) trials were conducted prior to and subsequent to the chronic treatment regimen. Marked baseline differences in plus-maze performance were present in the first experiment. A second experiment used a matched-pairs design to minimize preexisting differences. Results supported the hypothesis that EGb 761 may serve as an antistress buffer, attenuating the increase in anxiety typically observed in animals after cold water exposure. Tissue samples from the hippocampus and cortex were analyzed by Western blot for the transcription factor cyclic-AMP response element binding (CREB) protein. EGb 761 had no significant effect on immunoreactivity to CREB from either the hippocampus or the cerebral cortex.

Modafinil facilitates performance on a delayed nonmatching to position swim task in rats.

Modafinil is a wake-promoting drug approved by the FDA for the treatment of narcolepsy. Recent evidence suggests that modafinil may improve learning and memory processes. To further evaluate possible cognitive properties associated with modafinil, male Sprague-Dawley rats were tested in a delayed nonmatching to position (DNMTP) task. A modified water maze allowed animals to make one of two choices for the location of the escape platform. Each trial consisted of two swims. On the information swim (IS), only one choice was open to the animal for escape. One minute later, a choice swim (CS) presented the animal with two choices with the escape platform in the opposite position. There were 10 trials per day for 10 days. Rats received 0, 30, 55, or 100 mg/kg ip of modafinil 30 min prior to testing. Locomotor activity was also assessed. Animals that received 55 and 100 mg/kg made significantly more correct choices, indicating that higher doses of modafinil learned the task faster than did controls. While animals that received 100 mg/kg did exhibit an enhancement of locomotor activity, this effect did not result in more efficient goal-directed behavior. The evidence is consistent with previous research showing that modafinil facilitates cognitive processes.

The effects of cocaine on dietary self-selection in female rats

Cocaine was administered via an oral route to 18-h food deprived female rats for 14 consecutive days. Following administration of the drug or vehicle control each animal was presented with separate isocaloric rations of protein, fat, and carbohydrate in a dietary self-selection situation. Amounts consumed of each component were measured at 30 min, 60 min, 2 h, and 6 h following the drug treatment. The intake of all three macronutrients was suppressed by cocaine for 1 h. Between 2 and 6 h after administration, there was a compensatory increase in fat and carbohydrate, but not protein consumption. The results are discussed in terms of protein deficiency caused by cocaine in pregnant and/or lactating females being a causal factor in the deleterious effects on offspring.

One week of exposure to intermittent hypoxia impairs attentional set-shifting in rats

Intermittent hypoxia (IH), a characteristic of sleep apnea, was modeled in Fischer Brown Norway rats (10h/day for 7 days) followed by cognitive testing in an attentional set-shifting task. The ability to shift attention from one sensory modality (e.g., odor) to another (e.g., digging medium) was impaired, a finding that could not be attributed to deficits in attention, discrimination, learning, or motor performance. Instead, the deficit is likely to reflect impaired allocation of attentional resources of the working memory system.

Chronic sleep restriction impairs spatial memory in rats.

Although numerous experimental investigations have evaluated the neurobehavioral effects of either short periods of total sleep deprivation or selective rapid eye movement sleep deprivation, few studies have examined the effects of chronic sleep restriction (CSR). Long-Evans rats were deprived of sleep by the automated movement of activity wheels for 18 h/day for 5 consecutive days from 16:00 to 10:00 h, and were allowed 6 h/day of sleep opportunity (10:00–16:00 h; lights on from 10:00 to 22:00 h). Activity wheels were intermittently activated on a 3 s on : 12 s off schedule for the CSR condition, whereas a schedule of 36 min of continuous wheel movement in every 3 h was used for a cage movement control condition. A cross-over design was used with rats serving in both the CSR and the movement control conditions with 2 days of rest between conditions. Water maze acquisition training occurred at 16:00 h immediately after the 6-h sleep opportunity on each of the first 4 days, followed by a probe trial on day 5 to assess spatial memory recall. Although the rate of learning/acquisition was not affected by the daily 18 h of CSR, the day 5 recall of the platform location was impaired on three different probe trial measures. Thus, CSR impaired spatial memory, but did not affect the rate of learning/acquisition in the water maze.

A re-evaluation of the role of tetrahydropapaveroline in ethanol consumption in rats

The role of tetrahydropapaveroline (THP), a condensation product of a dopaldehyde with dopamine, in the regulation of alcohol consumption was investigated. In the first experiment, rats received intraventricular injections of either racemic THP hydrobromide (0.65 or 1.3 microg/microl), R-(+)-THP (0.66 or 1.4 microg/microl), or an equal volume of vehicle. The lower doses of both (+/-)-THP and (+)-THP significantly increased volitional alcohol intake. For the racemic compound, the increase was significant at 7-13% concentrations. The R-(+)-enantiomer increased consumption at 4-11 and 15-20% concentrations of ethanol. The higher doses of both compounds did not significantly alter alcohol preference. A second experiment evaluated the chronic effect of THP delivered subcutaneously via osmotic minipump. Animals receiving THP (0.1, 0.5, 1.0, 2.0, and 4.0 mg/ml) did not differ in their alcohol intake, compared to vehicle-treated controls. Whether or not endogenously formed THP participates in the etiology of alcohol addiction remains unclear. Nonetheless, there are few known compounds that induce a preference for unsweetened alcohol solutions over water in laboratory animals.

Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness

Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat multiple sleep latencies test (rMSLT), and the findings were compared to conventional polysomnographic measures of sleepiness. The 6 h of SD was produced by automated activity wheels, and was terminated at either the end of the light period or at the beginning of the dark period. The rMSLT consisted of 5 min wakefulness induced by sensory stimulation followed by 25 min of freedom to sleep. This procedure was repeated every 30 min for 3 h and was designed to minimize the amount of sleep lost due to the testing procedure. In separate rats, 6 h SD was followed by undisturbed recovery, allowing evaluation of conventional polysomnographic measures of sleepiness. Sleep onset latencies were reduced following SD, with recovery in the light (baseline = 8 min, 3 s versus post‐SD = 1 min, 17 s) and dark period (baseline = 14 min, 17 s versus 7 min, 7 s). Sleep onset latencies were not altered by varying the duration criterion for the first sleep bout (i.e., sleep bout length criteria of 10, 20, 30, or 60 s were compared). Polysomnographic variables (non‐rapid eye movement sleep episode duration, delta power, and number of awakenings) also provided reliable indirect measures of sleepiness, regardless of whether the recovery sleep occurred in the light or dark period. Evaluation of effect size indicated that the rMSLT was a strong measure of sleepiness, and was influenced by homeostatic, circadian, and illumination factors. The rMSLT provided a simple, objective, robust and direct measure of sleepiness that was as effective as conventional polysomnographic measures of sleepiness.

Handedness and Lateralised Tympanic Membrane Temperature in Relation to Approach-Avoidance Behaviour in Garnett's Bushbaby (Otolemur garnettii)

Studies of handedness suggest a relationship between hemispheric specialisation and emotional processing. Recently measures of lateralised tympanic membrane temperature (TMT) have identified similar relationships (i.e., the left hemisphere is involved in approach behaviour and the right hemisphere avoidance behaviour). In the present study we examined lateralised changes in TMT in response to social interaction in 10 Garnetts bushbabies. Additionally, we examined whether handedness could be used as a predictor of approach–avoidance tendencies. We found a positive association between temperature change and both allogrooming and affiliative approach. Social behaviour did not differ between right- and left-handed bushbabies. These findings are discussed in terms of existing theories of asymmetric emotional processing. Overall, the data suggest that there is a left hemisphere specialisation for processing approach-related behaviours, which is consistent with existing models of lateralised emotional processing. Our data also indicate that TMT is a reliable, cost-effective measure of cerebral activation that is less invasive and more practical than alternative measures such as EEG, PET, and fMRI.