Fos Expression In Brain Areas Research Articles

Effect of chronic alcohol vapor exposure on reinstatement of alcohol seeking induced by U50,488

Alcohol dependence and stress are associated with relapse to alcohol during abstinence, but the underlying mechanisms are poorly understood. Kappa opioid receptors (KOR) are involved in alcohol reward and in the effects of stress. Previously, in non-dependent rats, we showed that KOR in the bed nucleus of the stria terminalis (BNST) mediate reinstatement of alcohol seeking induced by the selective KOR agonist U50,488. Here, we determine the effects of chronic, intermittent exposure to alcohol vapor on U50,488-induced reinstatement of alcohol seeking. We also study brain mechanisms involved using the neuronal activity marker Fos and phosphorylated p38 MAPK (p-p38), an intracellular messenger implicated in the effects of KOR stimulation. We trained male Long-Evans rats to self-administer alcohol (12% w/v) and exposed them to alcohol vapor (14 h vapor/10 h air) daily for 24 d or to the control condition, extinguished alcohol-reinforced responding and determined the dose response for U50,488-induced reinstatement. We then determined the effects of vapor exposure on U50,488-induced Fos and p-p38 expression. Vapor-exposed rats were more sensitive to U50,488-induced reinstatement. U50,488 increased Fos expression in brain areas involved in stress-induced relapse, and Fos activation in the ventral BNST was greater in vapor exposed rats. Vapor exposed rats had increased basal p-p38 expression in the dorsal BNST, LC and NTS. Our findings suggest that changes in the neuronal responses to KOR stimulation in the ventral BNST may be involved in the increased sensitivity to U50,488 accompanying dependence.

Offspring's hydromineral adaptive responses to maternal undernutrition during lactation.

Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams' restriction.

Airjet and FG-7142-induced Fos expression differs in rats selectively bred for high and low anxiety-related behavior

We reported recently that two rat lines bred for either high (HAB) or low (LAB) anxiety-related behavior display differential Fos expression in restricted parts of the fear/anxiety circuitry when exposed to mild anxiety evoked in exploratory anxiety tests. Since different forms of anxiety are thought to activate different parts of the anxiety circuitry, we investigated now whether (1) an aversive stimulus which elicits escape behavior (airjet) and (2) the anxiogenic/panicogenic drug FG-7142 would reveal further differences in Fos expression as a marker of neuronal activation between HAB and LAB rats. Both airjet exposure and FG-7142 induced Fos expression in both lines in various anxiety-related brain areas. HAB rats, which displayed exaggerated escape responses during airjet exposure, exhibited increased Fos expression in brain areas including the hypothalamus, periaqueductal gray and locus coeruleus, as well as blunted Fos activation in the cingulate cortex in response to airjet and/or FG-7142. The results corroborate previous findings showing that trait anxiety affects neuronal excitability in hypothalamic and medial prefrontal areas. Furthermore, by using airjet as well as FG-7142, we now reveal that enhanced trait anxiety is also associated with neuronal hyperexcitability in the locus coeruleus and the periaqueductal gray, suggesting that investigation of an array of different anxiogenic stimuli is important for the detection of altered neuronal processing in trait anxiety.

Effects of galanin-like peptide (GALP) on locomotion, reproduction, and body weight in female and male mice

Galanin-like peptide (GALP) has been implicated in the neuroendocrine regulation of both feeding and reproduction. In male rodents and primates, intracerebroventricular (icv) infusions of GALP stimulate luteinizing hormone (LH) release, induce Fos expression in brain areas implicated in feeding and reproduction, and affect food intake and body weight in rodents. In gonad-intact and castrated male rats, icv administration of GALP also stimulates male sexual behavior. While the effects of GALP on male physiology and behavior are well documented, no studies have addressed such a role of GALP in females. We tested the effects of icv GALP infusions on LH release, locomotor activity, motor control, and body weight regulation in adult ovariectomized female mice hormonally primed with estradiol benzoate and progesterone. In addition, sexually-experienced male and female mice were treated with GALP and tested for sexual behavior. In females, GALP reduced open-field locomotor activity, the ability to maintain grip on an accelerating rotarod, and 24-h body weight in a dose-dependent manner. GALP also increased LH secretion in female mice, an effect that was blocked by pre-treatment with Antide, a gonadotropin-releasing hormone (GnRH) type-1 receptor antagonist. GALP infusions slightly decreased the occurrence of lordosis behavior in female mice and significantly increased the latencies with which females displayed receptivity. Unlike previous reports in male rats, GALP inhibited male sexual behavior in mice. Our data indicate that in female mice, GALP stimulates LH release via GnRH, and decreases body weight, motor control, and locomotor activity via GnRH-independent pathways. Furthermore, our sexual behavior and locomotor findings suggest species-specific differences in the mechanism and/or location of GALP action in the brains of rats and mice.

Forebrain c- fos expression under conditions conducive to pair bonding in female prairie voles ( Microtus ochrogaster)

Repeated mating over a period of 6 h facilitates pair-bond formation in monogamous prairie voles. Using this paradigm, we examined fos expression in brain areas implicated in social behavior in voles. We hypothesized that the presence of the fos protein after a period of time sufficient for pair bonding to occur may indicate brain areas that are especially important in pair bond formation. We found elevated levels of fos immunoreactivity in the medial and cortical amygdala, medial preoptic area (MPOA), and bed nucleus of the stria terminalis (BNST) in females that mated several times over a 6-h period as compared to a variety of unmated controls. No treatment effects were found in the central amygdala, nucleus accumbens (NAcc), or lateral septum (LS). We suggest that areas that show evidence of fos expression after sufficient time for pair bonding to occur may be important in the formation of associations between the partner and mating stimuli.

Developmental changes in c- fos expression to an age-specific social stressor in infant rats

Young rats become immobile when exposed to a potentially infanticidal adult male rat. Male-induced immobility declines during the preweaning period, paralleling the decrease in infanticidal threat. To investigate the neural substrates underlying the developmental change in immobility, male-induced expression of the immediate-early gene c- fos was assessed on postnatal days 7, 14 and 21. A huddle of three young rats was exposed to an adult male behind a screen. As control, three littermates were put in the testing chamber but not exposed to the male. On day 7, male exposed and control pups were immobile most of the time and c- fos expression did not differ between conditions. On day 14, rats in the presence of the male stopped ongoing behaviors and became immobile. They had significantly higher c- fos expression in the paraventricular nucleus of the hypothalamus, the amygdala, the periaqueductal gray, and the locus ceruleus. On day 21, the male-exposed rats that were immobile had elevated c- fos expression in a similar pattern as on day 14, however, different nuclei of the amygdala were activated. In contrast, male-exposed 21-day-old rats that showed control levels of immobility did not have elevated c- fos expression in these areas. These results demonstrate that male exposure induced c- fos expression in brain areas of young rats in an age-specific pattern. Some of the activated brain areas seem to have contributed to immobility. Differential activation of neuronal populations may underlie developmental changes in defensive immobility during early ontogeny.

Rhythms in Fos expression in brain areas related to the sleep-wake cycle in the diurnal Arvicanthis niloticus.

Most mammals show daily rhythms in sleep and wakefulness controlled by the primary circadian pacemaker, the suprachiasmatic nucleus (SCN). Regardless of whether a species is diurnal or nocturnal, neural activity in the SCN and expression of the immediate-early gene product Fos increases during the light phase of the cycle. This study investigated daily patterns of Fos expression in brain areas outside the SCN in the diurnal rodent Arvicanthis niloticus. We specifically focused on regions related to sleep and arousal in animals kept on a 12:12-h light-dark cycle and killed at 1 and 5 h after both lights-on and lights-off. The ventrolateral preoptic area (VLPO), which contained cells immunopositive for galanin, showed a rhythm in Fos expression with a peak at zeitgeber time (ZT) 17 (with lights-on at ZT 0). Fos expression in the paraventricular thalamic nucleus (PVT) increased during the morning (ZT 1) but not the evening activity peak of these animals. No rhythm in Fos expression was found in the centromedial thalamic nucleus (CMT), but Fos expression in the CMT and PVT was positively correlated. A rhythm in Fos expression in the ventral tuberomammillary nucleus (VTM) was 180 degrees out of phase with the rhythm in the VLPO. Furthermore, Fos production in histamine-immunoreactive neurons of the VTM cells increased at the light-dark transitions when A. niloticus show peaks of activity. The difference in the timing of the sleep-wake cycle in diurnal and nocturnal mammals may be due to changes in the daily pattern of activity in brain regions important in sleep and wakefulness such as the VLPO and the VTM.