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Systemic immune function is impaired by sleep restriction. However, the impact of sleep restriction on local immune responses and to what extent any impairment can be mitigated by nutritional supplementation is unknown. We assessed the effect of 72-h sleep restriction (2-h nightly sleep) on local immune function and skin barrier restoration of an experimental wound, and determined the influence of habitual protein intake (1.5 g·kg−1·day−1) supplemented with arginine, glutamine, zinc sulfate, vitamin C, vitamin D3, and omega-3 fatty acids compared with lower protein intake (0.8 g·kg−1·day−1) without supplemental nutrients on these outcomes. Wounds were created in healthy adults by removing the top layer of less than or equal to eight forearm blisters induced via suction, after adequate sleep (AS) or 48 h of a 72-h sleep restriction period (SR; 2-h nightly sleep). A subset of participants undergoing sleep restriction received supplemental nutrients during and after sleep restriction (SR+). Wound fluid was serially sampled 48 h postblistering to assess local cytokine responses. The IL-8 response of wound fluid was higher for AS compared with SR [area-under-the-curve (log10), 5.1 ± 0.2 and 4.9 ± 0.2 pg/ml, respectively; P = 0.03]; and both IL-6 and IL-8 concentrations were higher for SR+ compared with SR ( P < 0.0001), suggestive of a potentially enhanced early wound healing response. Skin barrier recovery was shorter for AS (4.2 ± 0.9 days) compared with SR (5.0 ± 0.9 days) ( P = 0.02) but did not differ between SR and SR+ ( P = 0.18). Relatively modest sleep disruption delays wound healing. Supplemental nutrition may mitigate some decrements in local immune responses, without detectable effects on wound healing rate. NEW & NOTEWORTHY The data herein characterizes immune function in response to sleep restriction in healthy volunteers with and without nutrition supplementation. We used a unique skin wound model to show that sleep restriction delays skin barrier recovery, and nutrition supplementation attenuates decrements in local immune responses produced by sleep restriction. These findings support the beneficial effects of adequate sleep on immune function. Additional studies are necessary to characterize practical implications for populations where sleep restriction is unavoidable.

Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD50) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD50 of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD50s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity.

Several experiments explored the roles of nucleus accumbens (NA), ventral pallidum (VP) and medial preoptic area (MPOA) in the regulation of maternal behavior in rats. A preliminary experiment found that bilateral radiofrequency lesions of medial NA did not disrupt maternal behavior. Experiment 1 found that bilateral infusions of muscimol into VP, but not into medial NA, reversibly disrupted maternal behavior. Experiment 2 found that unilateral muscimol injections into VP disrupted maternal behavior to a greater extent when paired with a contralateral N-methyl-d-aspartic acid (NMDA) MPOA lesion than when paired with a sham MPOA lesion. Experiment 3 showed that a unilateral NMDA MPOA lesion paired with a contralateral NMDA VP lesion (Contra group) disrupted maternal behavior to a much greater extent than did sham NMLA lesions or NMDA lesions of MPOA and VP ipsilateral to one another. Experiment 3 focused on the specificity of the maternal behavior disruptions and found that the primary maternal deficit in the Contra females was a severe deficit in retrieval behavior. Importantly, these females showed normal hoarding behavior, home cage activity, and elevated plus maze activity. Experiment 3 used Neu N immunohistochemistry to define the extent of MPOA and VP excitotoxic lesions. It is hypothesized that MPOA acts to facilitate the active components of maternal behavior by inhibiting NA, which then releases VP from GABAergic inhibition, and such disinhibition of VP allows pup stimuli to trigger appropriate maternal responses.

The medial preoptic area (MPOA), ventral pallidum (VP), and nucleus accumbens (NA) receive dopaminergic afferents and are involved in maternal behavior. Experiments investigated whether dopamine (DA) receptor antagonism in NA disrupts maternal behavior, determined the type of DA receptor involved, and investigated the involvement of drug spread to VP or MPOA. Injection of SCH 23390 (D1 DA receptor antagonist) into NA of postpartum rats disrupted retrieving at dosage levels that were ineffective when injected into MPOA or VP. Motor impairment was not the cause of the deficit. Injection of eticlopride (D2 DA receptor antagonist) into NA or VP was without effect. Results emphasize the importance of DA action on D1 receptors in NA for retrieval behavior.

Emotional hyperreactivity can inhibit maternal responsiveness in female rats and other animals. Maternal behavior in postpartum rats is disrupted by increasing norepinephrine release in the ventral bed nucleus of the stria terminalis (BSTv) with the α2-autoreceptor antagonist, yohimbine, or the more selective α2-autoreceptor antagonist, idazoxan (Smith et al., 2012). Because high noradrenergic activity in the BSTv can also increase anxiety-related behaviors, increased anxiety may underlie the disrupted mothering of dams given yohimbine or idazoxan. To assess this possibility, anxiety-related behaviors in an elevated plus maze were assessed in postpartum rats after administration of yohimbine or idazoxan. It was further assessed if the α2-autoreceptor agonist clonidine (which decreases norepinephrine release) would, conversely, reduce dams' anxiety. Groups of diestrous virgins were also examined. It was found that peripheral or intra-BSTv yohimbine did increase anxiety-related behavior in postpartum females. However, BSTv infusion of idazoxan did not reproduce yohimbine's anxiogenic effects and anxiety was not reduced by peripheral or intra-BSTv clonidine. Because yohimbine is a weak 5HT1A receptor agonist, other groups of females received BSTv infusion of the 5HT1A receptor agonist 8OH-DPAT, but it did not alter their anxiety-related behavior. Lastly, levels of norepinephrine and serotonin in tissue punches from the BSTv did not differ between postpartum and diestrous rats, but serotonin turnover was lower in mothers. These results suggest that the impaired maternal behavior after BSTv infusion of yohimbine or idazoxan cannot both be readily explained by an increase in dams' anxiety, and that BSTv α2-autoreceptor modulation alone has little influence on anxiety-related behaviors in postpartum or diestrous rats.

Maternal behavior in laboratory rats requires a network of brain structures including the ventral bed nucleus of the stria terminalis (BSTv) and medial preoptic area (mPOA). Neurotransmitter systems in the BSTv and mPOA influencing maternal behaviors are not well understood, although norepinephrine is an excellent candidate because the BSTv contains the densest noradrenergic fiber plexus in the forebrain and norepinephrine in the mPOA is known to influence other female reproductive functions.We hypothesized that downregulated noradrenergic activity in the BSTv and mPOA is necessary for mothering.Postpartum mother-litter interactions were observed after BSTv infusion of yohimbine (an α2 autoreceptor antagonist that increases norepinephrine release), and after BSTv or mPOA infusion of the more selective α2 autoreceptor antagonist idazoxan. Lastly, noradrenergic input to the BSTv/mPOA was selectively lesioned in nulliparous rats with anti-DBH-saporin to determine if this would facilitate mothering.BSTv yohimbine almost abolished retrieval of pups but did not significantly affect dams' ability to initiate contact, lick, or nurse them. BSTv idazoxan disrupted retrieval somewhat less than yohimbine, but significantly reduced nursing. mPOA idazoxan impaired retrieval more severely than that found after BSTv infusion. Anti-DBH-saporin almost eliminated noradrenergic terminals in the BSTv and reduced them by over 60% in the mPOA, but did not promote maternal responding. It also did not affect females' anxiety-related behavior.Downregulated noradrenergic activity in the BSTv and mPOA is necessary for postpartum maternal behavior in rats, but eliminating this system alone is insufficient to promote maternal behaviors in nulliparous females.

The postpartum period is associated with many behavioral changes, including a reduction in anxiety, which is thought to be necessary for mothers’ ability to appropriately care for infants. In laboratory rats, this reduction in anxiety requires recent contact with pups, but areas of the brain where infant contact influences neural activity to reduce anxiety are mostly unknown. We examined c-fos expression in lactating rats whose pups were removed for 4 h to increase mothers’ anxiety, or not removed to maintain low anxiety in mothers, followed by exposure to the anxiogenic stimuli of either brief handling or handling followed by exposure to an elevated plus maze. Control animals had their litters removed or not, but no further stimulation. A large number of neural sites traditionally implicated in regulating anxiety in male rats were examined, and similar to what is found in male rats, most showed increased Fos expression after handling and/or elevated plus-maze exposure. Litter presence before testing affected Fos expression due to handling or elevated plus-maze exposure only in the ventral bed nucleus of the stria terminalis, dorsal and ventral preoptic area, ventromedial hypothalamus, lateral habenula, and supramammillary nucleus. Contrary to expectations, prior litter presence was associated with more Fos expression in most of these sites after handling and/or elevated plus-maze stimulation, and only after such stimulation. These sites may be of particular importance for how sensory inputs from infants modulate anxiety and other mood states during the postpartum period.

Reports an error in "Noradrenergic alpha-2 receptor modulators in the ventral bed nucleus of the stria terminalis: Effects on anxiety behavior in postpartum and virgin female rats" by Carl D. Smith, Christopher C. Piasecki, Marcus Weera, Joshua Olszewicz and Joseph S. Lonstein (Behavioral Neuroscience, 2013[Aug], Vol 127[4], 582-597). Table 2 should have used the ratio of 5HIAA/serotonin - rather than the inverse - as the indicator of serotonin turnover. Using the correct ratio, differences in serotonin turnover between the postpartum and virgin females are: BSTv - 1.11 0.06 vs 0.79 0.11 (t 2.57, p 0.05); BSTd - 1.01 0.07 vs 0.68 0.11 (t 2.58, p 0.05). That is, contrary to what was originally reported, postpartum females had higher serotonin turnover in both subregions of the BST compared to virgins. The penultimate sentence in the abstract noting serotonin turnover in mothers has been corrected in the online version of this article. (The following abstract of the original article appeared in record 2013-22430-001.) Emotional hyperreactivity can inhibit maternal responsiveness in female rats and other animals. Maternal behavior in postpartum rats is disrupted by increasing norepinephrine release in the ventral bed nucleus of the stria terminalis (BSTv) with the α2-autoreceptor antagonist, yohimbine, or the more selective α2-autoreceptor antagonist, idazoxan (Smith et al., 2012). Because high noradrenergic activity in the BSTv can also increase anxiety-related behaviors, increased anxiety may underlie the disrupted mothering of dams given yohimbine or idazoxan. To assess this possibility, anxiety-related behaviors in an elevated plus maze were assessed in postpartum rats after administration of yohimbine or idazoxan. It was further assessed if the α2-autoreceptor agonist clonidine (which decreases norepinephrine release) would, conversely, reduce dams' anxiety. Groups of diestrous virgins were also examined. It was found that peripheral or intra-BSTv yohimbine did increase anxiety-related behavior in postpartum females. However, BSTv infusion of idazoxan did not reproduce yohimbine's anxiogenic effects and anxiety was not reduced by peripheral or intra-BSTv clonidine. Because yohimbine is a weak 5HT1A receptor agonist, other groups of females received BSTv infusion of the 5HT1A receptor agonist 8OH-DPAT, but it did not alter their anxiety-related behavior. Lastly, levels of norepinephrine and serotonin in tissue punches from the BSTv did not differ between postpartum and diestrous rats, but serotonin turnover was higher in mothers. These results suggest that the impaired maternal behavior after BSTv infusion of yohimbine or idazoxan cannot both be readily explained by an increase in dams' anxiety, and that BSTv α2-autoreceptor modulation alone has little influence on anxiety-related behaviors in postpartum or diestrous rats.