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Brain injury survivors, particularly those injured early in life are very likely to abuse drugs and alcohol later in life. Alcohol abuse following traumatic brain injury (TBI) is associated with poorer rehabilitation outcomes and a greatly increased chance of suffering future head trauma. Thus, substance abuse among persons with brain injury reduces the chances for positive long-term outcomes and greatly increases the societal costs. In this review, we discuss the evidence for modulation of drinking behavior after TBI and the costs of problem drinking after TBI from both a biomedical and economic perspective. Further, we review the existing animal models of drinking after brain injury and consider the potential underlying psychosocial and neurobiological mediators of this phenomenon. In particular, we highlight the potential interactions among TBI, neuroinflammation and alcohol abuse. Substance abuse is a major problem in this vulnerable patient population and a greater understanding of the underlying biology has the potential to greatly improve outcomes. [ABSTRACT FROM AUTHOR]

Most adult humans have been infected with Epstein–Barr virus (EBV) and carry the latent virus. The EBV genome codes for several proteins that form an early antigen complex important for viral replication; one of these proteins is deoxyuridine triphosphate nucleotidohydrolase (dUTPase). The EBV-encoded dUTPase can induce sickness responses in mice. Because stress can increase latent virus reactivation, we hypothesized that chronic restraint would exacerbate sickness behaviors elicited by EBV-encoded dUTPase. Male Swiss-Webster mice were injected daily for 15 days with either saline or EBV-encoded dUTPase. Additionally, half of the mice from each condition were either restrained for 3 h daily or left undisturbed. Restraint stress impaired learning and memory in the passive avoidance chamber; impaired learning and memory was due to EBV-encoded dUTPase injected into restrained mice. EBV-encoded dUTPase induced sickness responses and restraint stress interacts with EBV-encoded dUTPase to exacerbate the sickness response. These data support a role for EBV-encoded dUTPase and restraint stress in altering the pathophysiology of EBV independent of viral replication. [ABSTRACT FROM AUTHOR]

Highlights: [•] Prenatal restraint and postnatal melatonin increased depressive-like responses. [•] Prenatal restraint increased the number of fecal boli during the forced swim test. [•] Prenatal restraint reduced CA1 dendritic branching. [•] Perinatal melatonin protected hamsters from this restraint-induced reduction. [Copyright &y& Elsevier]

Highlights: [•] Sexual experience during adolescence but not adulthood increases alcohol self-administration. [•] Sexual experience increased anxiety- and depressive-like behaviors. [•] Adolescent experiences have enduring effects on adult phenotype. [Copyright &y& Elsevier]

Abstract: This study examined the photoperiodic regulation of energy balance and cannabinoid receptor expression in the Siberian hamster (Phodopus sungorus) hypothalamus. Short day lengths, beginning at weaning, reduced food intake, body mass and fat pad masses and also decreased cannabinoid receptor immunostaining in the anterior and lateral hypothalamic nuclei of male hamsters. These data suggest a potential role for reduced cannabinoid drive in mediating short day-induced alterations in energy balance. [Copyright &y& Elsevier]

Abstract: Much of the permanent damage that occurs in response to nervous system damage (trauma, infection, ischemia, etc.) is mediated by endogenous secondary processes that can contribute to cell death and tissue damage (excitotoxicity, oxidative damage and inflammation). For humans to evolve mechanisms to minimize secondary pathophysiological events following CNS injuries, selection must occur for individuals who survive such insults. Two major factors limit the selection for beneficial responses to CNS insults: for many CNS disease states the principal risk factor is advanced, post-reproductive age and virtually all severe CNS traumas are fatal in the absence of modern medical intervention. An alternative hypothesis for the persistence of apparently maladaptive responses to CNS damage is that the secondary exacerbation of damage is the result of unavoidable evolutionary constraints. That is, the nervous system could not function under normal conditions if the mechanisms that caused secondary damage (e.g., excitotoxicity) in response to injury were decreased or eliminated. However, some vertebrate species normally inhabit environments (e.g., hypoxia in underground burrows) that could potentially damage their nervous systems. Yet, neuroprotective mechanisms have evolved in these animals indicating that natural selection can occur for traits that protect animals from nervous system damage. Many of the secondary processes and regeneration-inhibitory factors that exacerbate injuries likely persist because they have been adaptive over evolutionary time in the healthy nervous system. Therefore, it remains important that researchers consider the role of the processes in the healthy or developing nervous system to understand how they become dysregulated following injury. [Copyright &y& Elsevier]

Abstract: This study examined photoperiodic regulation of affective behaviours in collared lemmings (Dicrostonyx groenlandicus). Male and female lemmings were housed in either long (LD 22:2), intermediate (LD 16:8), or short days (LD 8:16) for 9 weeks. Exposure to short days induced moult to a winter pelage and gonadal regression in male, but not female, lemmings. Lemmings housed in long days reduced anxiety-like responses in the elevated plus maze. Depressive-like behaviours were decreased in the intermediate photoperiod relative to other photoperiod groups. [Copyright &y& Elsevier]

Abstract: d-serine and d-aspartate are important regulators of mammalian physiology. d-aspartate is found in nervous and endocrine tissue, specifically in hypothalamic supraoptic and paraventricular nuclei, pituitary, and adrenal medullary cells. Endogenous d-aspartate is selectively degraded by d-aspartate oxidase. We previously reported that adult male mice lacking the gene for d-aspartate oxidase (Ddo −/− mice) display elevated concentrations of d-aspartate in several neuronal and neuroendocrine tissues as well as impaired sexual performance and altered autogrooming behaviour. In the present study, we analyzed behaviours relevant to affect, cognition, and motor control in Ddo −/− mice. Ddo −/− mice display deficits in sensorimotor gating and motor coordination as well as reduced immobility in the forced swim test. Basal corticosterone concentrations are elevated. The Ddo −/− mice have d-aspartate immunoreactive cells in the cerebellum and adrenal glands that are not observed in the wild-type mice. However, no differences in anxiety-like behaviour are detected in open field or light–dark preference tests. Also, Ddo −/− mice do not differ from wild-type mice in either passive avoidance or spontaneous alternation tasks. Although many of these behavioural deficits may be due to the lack of Ddo during development, our results are consistent with the widespread distribution of d-aspartate and the hypothesis that endogenous d-aspartate serves diverse behavioural functions. [Copyright &y& Elsevier]

Abstract: Lactating females direct aggressive behaviors towards intruders presumably to reduce the likelihood of infanticide of their pups. Infected animals display a constellation of responses that include lethargy, anorexia, and decreased social interactions. This suite of responses is referred to as sickness behavior, and is putatively part of an adaptive strategy to aid the organism in recovery from infection. Previous work has suggested that animals can suppress the behavioral symptoms of sickness in order to engage in adaptive behaviors. To test whether adaptive nest defense is affected by illness, dams received a peripheral injection of either saline or lipopolysaccharide (LPS [50, 400, or 1000 μg/kg]), a non-replicating component of bacterial cell walls that activates the immune system. Simulated infection with LPS reduced body mass and food intake in dams and interfered with litter growth in a dose-dependent manner. Generally, nest defense was unaffected by LPS; the proportion of dams displaying maternal aggression against a male intruder, as well as the latency and duration of aggressive encounters were only suppressed at the highest LPS dose tested. Further, LPS treatment also altered non-agonistic behavior during the aggression test as indicated by reduced social investigation of the intruder and an increased time spent immobile during the session. LPS administration also significantly increased serum corticosterone concentrations in lactating females. These findings suggest that maternal aggression is not suppressed by LPS-evoked immune activation at doses that attenuate other aspects of maternal and social behavior. [Copyright &y& Elsevier]

Abstract: Although critical for transducing seasonal information, melatonin has also been implicated in several physiological systems, as well as the regulation of behavioral and cognitive processes. Therefore, we investigated the neurobehavioral effects of mice missing the type 1 melatonin receptor (MT1). Male and female MT1 knockout (MT1−/−) and wild-type (WT) mice were tested in the acoustic startle/prepulse inhibition (PPI), open field and Porsolt forced swim tests. Male and female MT1−/− mice displayed dramatically impaired prepulse inhibition in the acoustic startle response. Female WT mice were more active in the open field than WT males. However, male and female MT1−/− mice did not differ in total locomotor activity. WT animals spent significantly more time in the center of the arena (a behavioral outcome associated with reduced anxiety-like behavior) than MT1−/− mice. Also, the sex difference between male and female WT mice in the amount of time spent in the center versus periphery was not observed among MT1−/− mice. Both male and female MT1−/− mice significantly increased the time spent immobile in the forced swim test, an indication of depressed-like behavior. The lifetime lack of MT1 signaling contributes to behavioral abnormalities including impairments in sensorimotor gating and increases in depressive-like behaviors. Taken together, MT1 receptor signaling may be important for normal brain and behavioral function. [Copyright &y& Elsevier]

Abstract: Most organisms display circadian rhythms that coordinate complex physiological and behavioral processes to optimize energy acquisition, storage, and expenditure. Disruptions to the circadian system with environmental manipulations such as nighttime light exposure alter metabolic energy homeostasis. Exercise is known to strengthen circadian rhythms and to prevent weight gain. Therefore, we hypothesized providing mice a running wheel for voluntary exercise would buffer against the effects of light at night (LAN) on weight gain. Mice were maintained in either dark (LD) or dim (dLAN) nights and provided either a running wheel or a locked wheel. Mice exposed to dim, rather than dark, nights increased weight gain. Access to a functional running wheel prevented body mass gain in mice exposed to dLAN. Voluntary exercise appeared to limit weight gain independently of rescuing changes to the circadian system caused by dLAN; increases in daytime food intake induced by dLAN were not diminished by increased voluntary exercise. Furthermore, although all of the LD mice displayed a 24h rhythm in wheel running, nearly half (4 out of 9) of the dLAN mice did not display a dominant 24h rhythm in wheel running. These results indicate that voluntary exercise can prevent weight gain induced by dLAN without rescuing circadian rhythm disruptions. [Copyright &y& Elsevier]

Highlights: [•] Concurrent deletion of nNOS and p47phox (NOX) alters behavior in mice. [•] nNOS and NOX deletions synergize to impair cognitive function. [•] Deletion of nNOS or NOX alone impairs social behavior. [•] Deletion of nNOS and NOX together enhances social preference. [•] Current findings may provide insight into schizophrenia and autism. [ABSTRACT FROM AUTHOR]

Abstract: Challenging conditions early in development can have enduring effects into adulthood. The effects of low temperatures were examined on subsequent sex-specific morphology (anogenital distance [AGD]), maternal care, and reproductive performance in adult female mice. Dams (F0) were maintained either in (1) standard laboratory room temperatures (21±2 °C) or (2) low temperatures (10±2 °C) throughout gestation. Their progeny (F1) either remained in the temperature condition in which they were conceived or were switched to the other temperature condition at 2 days of age until weaning. Reproductive performance and maternal behaviors were assessed in adulthood. F0 dams that were maintained in low temperatures bore larger litters as compared to F0 animals housed in standard temperatures throughout their pregnancy. In contrast, mean litter size was reduced for all groups of F1 females that experienced low temperatures. Infant mortality was elevated in litters of F1 females that were exposed to low temperatures both before and after birth. Prenatal exposure to low temperatures was associated with reduced responsiveness towards the nursing young and decreased maternal aggression in F1 animals. Prenatally treated F1 females had longer, male-like AGDs on Day 2 following birth compared to animals not subjected to experimental manipulations. Our results indicate that exposure to low temperatures during early development impairs reproductive function and is associated with important fitness costs as evidenced by reduced offspring survival. Our findings also suggest that chronic low temperatures experienced only after birth may have less deleterious effects than exposure to a combination of pre- and postnatal or prenatal treatments alone. [Copyright &y& Elsevier]

Traumatic brain injuries (TBIs) are a common and costly ongoing public health concern. Injuries that occur during childhood development can have particularly profound and long-lasting effects. One common consequence and potential mediator of negative outcomes of TBI is sleep disruption which occurs in a substantial proportion of TBI patients. These individuals report greater incidences of insomnia and sleep fragmentation combined with a greater overall sleep requirement meaning that many patients are chronically sleep-deprived. We sought to develop an animal model of developmental TBI-induced sleep dysfunction. Specifically, we tested the hypothesis that early (postnatal day 21), repeated closed head injuries in Swiss-Webster mice, would impair basal and homeostatic sleep responses in adulthood. Further, we asked whether environmental enrichment (EE), a manipulation that improves functional recovery following TBI and has been shown to alter sleep physiology, would prevent TBI-induced sleep dysfunction and alter sleep-modulatory peptide expression. In contrast to our hypothesis, the mild, repeated head injury that we used did not significantly alter basal or homeostatic sleep responses in mice housed in standard laboratory conditions. Sham-injured mice housed in enriched environments exhibited enhanced rapid eye movement (REM) sleep and expression of the REM-promoting peptide pro-melanin-concentrating hormone, an effect that was not apparent in TBI mice housed in enriched environments. Thus, TBI blocked the REM-enhancing effects of EE. This work has important implications for the management and rehabilitation of the TBI patient population. [ABSTRACT FROM AUTHOR]

Abstract: Individuals are increasingly exposed to light at night. Exposure to constant light (LL) disrupts circadian rhythms of locomotor activity, body temperature, hormones, and the sleep-wake cycle in animals. Other behavioural responses to LL have been reported, but are inconsistent. The present experiment sought to determine whether LL produces changes in affective responses and whether behavioural changes are mediated by alterations in glucocorticoid concentrations. Relative to conspecifics maintained in a light/dark cycle (LD, 16:8 light/dark), male Swiss-Webster mice exposed to LL for three weeks increased depressive-like behavioural responses as evaluated by the forced swim test and sucrose anhedonia. Furthermore, providing a light escape tube reversed the effects of LL in the forced swim test. LL mice displayed reduced anxiety as evaluated by the open field and elevated-plus maze. Glucocorticoid concentrations were reduced in the LL group suggesting that the affective behavioural responses to LL are not the result of elevated corticosterone. Additionally, mice housed in LD with a clear tube displayed increased paired testes mass as compared to LL mice. Taken together, these data provide evidence that exposure to unnatural lighting can induce significant changes in affect, increasing depressive-like and decreasing anxiety-like responses. [Copyright &y& Elsevier]

Highlights: [•] Luzindole injection increases serum melatonin concentrations. [•] 4-P-PDOT, an MT2 specific antagonist, does not affect serum melatonin. [•] Possible feedback control of pineal melatonin secretion, occurring through MT1. [ABSTRACT FROM AUTHOR]