![]() Amphetamine-induced hyperactivity is the most widely used rodent animal model to test the efficacy of antimanic therapeutics ( Young et al., 2011). A 72h rapid eye movement (REM) sleep deprivation (SD) produced in rats a transient period of hyperactivity and insomnia, two clinical symptoms of manic episodes, and has been suggested as a putative model of mania by Gessa et al. Nevertheless, and despite its obvious etiopathogenic relevance-given that SD is a triggering factor of manic episodes in bipolar patients ( Barbini et al., 1996)-SD has been less studied in the context of mania modeling, especially in terms of its predictive validity. Interestingly, more recent studies have shown that 96h of REM SD reduced neurogenesis in the dentate gyrus of the hippocampus of adult rats ( Guzman-Marin et al., 2005). Since neuroplasticity deficits have been associated with bipolar disorder ( Machado-Vieira et al., 2014), this SD model may lead to progress in understanding the neurobiological aspects of mania and to identification of new treatments. Increasing evidence suggests that the intracellular signaling molecule protein kinase C (PKC) may be involved in the etiology of bipolar disorder ( Abrial et al., 2011). Thus, abnormally-elevated PKC activity has been found in platelets from medication-free bipolar patients experiencing a manic episode ( Friedman et al., 1993 Hahn et al., 2005). Moreover, mood-stabilizers such as lithium and valproate have been reported to inhibit PKC activity both in vitro and in vivo ( Jensen and Mørk, 1997 Manji and Lenox, 1999). In rodents, the non-selective PKC inhibitor tamoxifen has been shown to reduce the hyperlocomotion elicited by amphetamine ( Einat et al., 2007 Sabioni et al., 2008). In addition, preliminary clinical trials demonstrating that tamoxifen rapidly improved manic symptoms of bipolar patients ( Bebchuk et al., 2000 Kulkarni et al., 2006 Zarate et al., 2007 Yildiz et al., 2008 Amrollahi et al., 2010) suggest that PKC inhibition might be a relevant antimanic strategy. In view of these elements, this study aimed to investigate the antimanic-like action of PKC inhibition in the SD model in rats. We first verified the validity of SD as a model of mania by assessing the effects of clinically-effective agents on behavioral consequences of SD. Second, we explored impaired adult hippocampal cell proliferation as a possible cellular mechanism underlying manic-like behaviors and its recovery by antimanic agents. The implications of such work are far reaching, as sleep research in preindustrial and developing societies is documenting natural sleep-wake patterns in previously inaccessible environments.And third, we examined the antimanic potential of both selective (chelerythrine) and non-selective (tamoxifen) PKC inhibitors and their effects on hippocampal cell proliferation in the SD model. Conclusion: We propose operational definitions for multiple dimensions of segmented sleep and conclude that actigraphy is an effective method for detecting segmented sleep in future cross-site comparative research. Moreover, of the 6 tested parameter settings to detect wake bouts, the setting where the sleep-wake algorithm was parameterized to detect 20 consecutive minutes throughout the designated sleep period did not overestimate or underestimate wake bouts, had the lowest mean difference, and did not significantly differ from reported wake-bout events. Results: Only 1 parameter setting could reliably detect reported naps (15-minute nap length, ≤50 counts). Using the Bland- Altman technique to determine concordance, we analyzed reported events of daytime napping and nighttime wake bouts. Measurements: Thirty-three subjects participated in the study for 393 observation days. Participants: The Hadza-a non-industrial foraging population. Setting: Equatorial Tanzania in January to February 2016. ![]() To identify settings that identify periods of wakefulness during sleep,we used data from a subsample of women who reported discrete wake bouts while nursing at night. Design: To identify parameter settings that best identify napping during periods of wakefulness, we analyzed 137 days on which participants reported daytime napping, as compared with a random subset of 30 days when no naps were reported. Objective: To compare different scoring parameter settings in actigraphy software for inferring sleep and wake bouts for validating analytical techniques outside of laboratory environments.
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