Effects of N-Methyl-D-Aspartate receptor blockade on cross-sensitization between D-Tyr11 neurotensin and amphetamine

Blockade of neurotensin (NT) receptors with SR-48692 prevents the development of sensitization to the locomotor activating effects of amphetamine (AMPH). In addition, repeated icv injections of NT or of its analog, D-Tyr 11 NT, sensitize animals to the locomotor activating effects of AMPH. Recent evidence indicates a role for glutamate (GLU) in the development of sensitization to psychostimulant drugs inasmuch as co-administration of GLU antagonists prevents induction of AMPH and cocaine sensitization. The present study was aimed at testing the hypothesis that endogenous glutamatergic systems also play a role in the induction of cross-sensitization between NT and AMPH. Experiments were performed on male rats implanted with a guide cannula above the left lateral ventricle. During the induction phase, locomotor activity was measured on four occasions every second day for two hours after an icv injection of 18nmol/10ol of D-Tyr 11 NT, or saline, preceded 30 min before by a systemic injection of CPP, [(+/-)-3-(2-carboxypiperazine-4-yl)-propanephosphonic] (4 mg/kg), a GLU antagonist, or its vehicle. One week after the induction phase, locomotor activity to a single injection of AMPH (0.75mg/kg) was measured in all rats (sensitization test). Results show that AMPH induced greater ambulatory activity in animals pretreated with D-Tyr 11 NT alone, a sensitization effect that was attenuated by CPP given during the induction phase. These results suggest that GLU may play a role in the development of cross-sensitization between D-Tyr 11 NT and AMPH

The influence of sleep on memory

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The effectiveness of exercise interventions targeting sleep in older adults with cognitive impairment or Alzheimer's disease and related dementias ( AD / ADRD ): A systematic review and meta‐analysis

Summary: Sleep loss is associated with reduced health and quality of life, and increased risk of Alzheimer's disease and related dementias. Up to 66% of persons with Alzheimer's disease and related dementias experience poor sleep, which can predict or accelerate the progression of cognitive decline. Exercise is a widely accessible intervention for poor sleep that can protect against functional and cognitive decline. No previous systematic reviews have investigated the effectiveness of exercise for sleep in older adults with mild cognitive impairment or Alzheimer's disease and related dementias. We systematically reviewed controlled interventional studies of exercise targeting subjectively or objectively (polysomnography/actigraphy) assessed sleep in persons with mild cognitive impairment or Alzheimer's disease and related dementias. We conducted searches in PubMed, Embase, Scopus and Cochrane‐Library (n = 6745). Nineteen randomised and one non‐randomised controlled interventional trials were included, representing the experiences of 3278 persons with mild cognitive impairment or Alzheimer's disease and related dementias. Ten had low‐risk, nine moderate‐risk, and one high‐risk of bias. Six studies with subjective and eight with objective sleep outcomes were meta‐analysed (random‐effects model). We found moderate‐ to high‐quality evidence for the beneficial effects of exercise on self‐reported and objectively‐measured sleep outcomes in persons with mild cognitive impairment or Alzheimer's disease and related dementias. However, no studies examined key potential moderators of these effects, such as sex, napping or medication use. Our results have important implications for clinical practice. Sleep may be one of the most important modifiable risk factors for a range of health conditions, including cognitive decline and the progression of Alzheimer's disease and related dementias. Given our findings, clinicians may consider adding exercise as an effective intervention or adjuvant strategy for improving sleep in older persons with mild cognitive impairment or Alzheimer's disease and related dementias

Overnight consolidation aids the transfer of statistical knowledge from the medial temporal lobe to the striatum

Sleep is important for abstraction of the underlying principles (or gist) which bind together conceptually related stimuli, but little is known about the neural correlates of this process. Here, we investigate this issue using overnight sleep monitoring and functional magnetic resonance imaging (fMRI). Participants were exposed to a statistically structured sequence of auditory tones then tested immediately for recognition of short sequences which conformed to the learned statistical pattern. Subsequently, after consolidation over either 30min or 24h, they performed a delayed test session in which brain activity was monitored with fMRI. Behaviorally, there was greater improvement across 24h than across 30min, and this was predicted by the amount of slow wave sleep (SWS) obtained. Functionally, we observed weaker parahippocampal responses and stronger striatal responses after sleep. Like the behavioral result, these differences in functional response were predicted by the amount of SWS obtained. Furthermore, connectivity between striatum and parahippocampus was weaker after sleep, whereas connectivity between putamen and planum temporale was stronger. Taken together, these findings suggest that abstraction is associated with a gradual shift from the hippocampal to the striatal memory system and that this may be mediated by SWS

Sleep spindles may predict response to cognitive behavioral therapy for chronic insomnia

Background While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed at determining whether sleep spindle density at pre-treatment predicts treatment response to cognitive behavioral therapy for insomnia. Methods Twenty-four participants with chronic primary insomnia took part in a 6-week cognitive behavioral therapy for insomnia performed in groups of 4 to 6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment and at 3- and 12-months follow-up assessments. Secondary outcome measures were extracted from sleep diaries over seven days and one overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stages N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive behavioral therapy. Results After adjusting for age, sex and education level, lower spindle density at pre-treatment predicted poorer response over the 12-months follow-up, as reflected by smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. Conclusion These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to cognitive behavioral therapy

Changes in recognition memory over time: an ERP investigation into vocabulary learning

Although it seems intuitive to assume that recognition memory fades over time when information is not reinforced, some aspects of word learning may benefit from a period of consolidation. In the present study, event-related potentials (ERP) were used to examine changes in recognition memory responses to familiar and newly learned (novel) words over time. Native English speakers were taught novel words associated with English translations, and subsequently performed a Recognition Memory task in which they made old/new decisions in response to both words (trained word vs. untrained word), and novel words (trained novel word vs. untrained novel word). The Recognition task was performed 45 minutes after training (Day 1) and then repeated the following day (Day 2) with no additional training session in between. For familiar words, the late parietal old/new effect distinguished old from new items on both Day 1 and Day 2, although response to trained items was significantly weaker on Day 2. For novel words, the LPC again distinguished old from new items on both days, but the effect became significantly larger on Day 2. These data suggest that while recognition memory for familiar items may fade over time, recognition of novel items, conscious recollection in particular may benefit from a period of consolidation

Short and long sleepers: a difference in sleep capacity or in the tolerance of sleep pressure?

Objectives Sleep duration varies greatly among individuals. Whether this variation has a biological basis is largely unknown. Here we compared two extreme phenotypic groups, short sleepers and long sleepers. We tested 1) whether there is difference in the maximal sleep capacity between the two groups, or 2) whether there is a difference in the tolerance of homeostatic sleep pressure as measured on the basis of cognitive performance. Methods Healthy young (18-30 y) individuals who based on actigraphy were either short sleepers (n=7, habitual bedrest 9 h) underwent a 28-day inpatient protocol, including 4 days of habitual sleep (HS), 20 days of extended (12 h) sleep opportunities, a 36-h sleep deprivation (SD) period, and 2 days of recovery sleep. Total sleep time (TST) was quantified daily with polysomnography, and performance with the psychomotor vigilance task (PVT) several times every wake episode. Performance variables included number of lapses (reaction times, RT > 500 ms), median speed (1/RT), and interpercentile (IPR) range (difference between 90th and 10th percentile in 1/RT). Results In the HS condition, TST was 5.8 h in the short sleepers and 8.9 h in the long sleepers (p < 0.001). At the end of the sleep extension protocol (average of last three nights), daily TST was 8.5 h in the short sleepers and 8.8 h in the long sleepers (n.s.). None of the PVT measures differed between the two groups in the HS condition. When given extended sleep opportunities, PVT performance improved in the short sleepers (p < 0.001) but not in the long sleepers. Two-hourly PVTs during the SD revealed that short sleepers showed fewer lapses (p < 0.001) and a smaller IPR (p < 0.04) than the long sleepers, particularly in the latter part of the SD. Conclusion The maximal sleep capacity of young healthy adults is approximately 8.9 h. The disparity in habitual sleep duration between short and long sleepers appears to reflect a trait-like difference in the tolerance of homeostatic sleep pressure rather than in the capacity to sleep. Short sleepers seem to possess a ´cognitive reserve´ that becomes apparent at very low and very high levels of sleep pressure