Significant Increase In Fos Expression Research Articles

Defensive behaviors and brain regional activation changes in rats confronting a snake

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

Effects of lateral olfactory tract stimulation on Fos immunoreactivity in vasopressin neurones of the rat piriform cortex.

In the main olfactory system, odours are registered at the main olfactory epithelium and are then processed at the main olfactory bulb (MOB) and, subsequently, by the anterior olfactory nucleus (AON), the piriform cortex (PC) and the cortical amygdala. Previously, we reported populations of vasopressin neurones in different areas of the rat olfactory system, including the MOB, accessory olfactory bulb (AOB) and the AON and showed that these are involved in the coding of social odour information. Utilising immunohistochemistry and a transgenic rat in which an enhanced green fluorescent protein reporter gene is expressed in vasopressin neurones (eGFP-vasopressin), we now show a population of vasopressin neurones in the PC. The vasopressin neurones are predominantly located in the layer II of the PC and the majority co-express the excitatory transmitter glutamate. Furthermore, there is no sex difference in the number of neurones expressing vasopressin. Electrical stimulation of the lateral olfactory tract leads to a significant increase in the number of Fos-positive nuclei in the PC, MOB, AOB, dorsal AON and supraoptic nucleus (SON). However, there was only a significant increase in Fos expression in vasopressin cells of the PC and SON. Thus, functionally distinct populations of vasopressin cells are implicated in olfactory processing at multiple stages of the olfactory pathway.

Stress alters asenapine-induced Fos expression in the Meynert’s nucleus: response of adjacent hypocretin and melanin-concentrating hormone neurons in rat

Objective: Asenapine (ASE), an atypical antipsychotic drug used in the treatment of schizophrenia, induces Fos expression in forebrain. Effect of ASE on activity of basal nucleus of Meynert (NBM) cells, a part of the striatal–cortical circuits, was studied. We were also interested to reveal whether a chronic unpredictable variable mild stress (CMS) preconditioning might affect the ASE impact.Methods: Rats were divided into as follows: controls-vehicle, controls-ASE, stressed-vehicle and stressed-ASE groups. CMS included restrain, social isolation, crowding, swimming and cold applied for 21 days. On the 22nd day, rats were subcutaneously injected with ASE (0.3 mg/kg) or vehicle (saline 300 μl/rat), 90 min prior euthanizing. After transcardial fixation, brains were cut into 30 μm thick coronal sections. Fos protein presence, as indicator of cell activity, was detected by ABC immunohistochemistry. Hypocretin (Hcrt) and melanin-concentrating hormone (MCH) containing cells were visualized with fluorescent dyes.Results: ASE induced significant increase in Fos expression in NBM in both controls and CMS preconditioned rats in comparison with the related vehicle-treated controls. CMS preconditioning, however, significantly lowered the Fos response to ASE in NBM. From Hrct and MCH cells, only Hcrt ones displayed Fos presence in response to ASE.Discussion: This study demonstrates for the first time that ASE may target a special group of cells occupying NBM, which effect can be modulated by CMS preconditioning. This finding extends a view that ASE impact may extend beyond the classical forebrain target areas common for the action of all antipsychotics and might be helpful in the identification of sites and side effects of its therapeutic actions.

Peripheral administration of palmitoylated prolactin-releasing peptide induces Fos expression in hypothalamic neurons involved in energy homeostasis in NMRI male mice

Energy homeostasis is the result of a balance between energy intake and expenditure, and the hypothalamus plays a key role in the regulation of these processes. The hypothalamic prolactin-releasing peptide (PrRP) is involved in food intake regulation and energy homeostasis, although only its lipidized analogs exert central anorexigenic effects after peripheral administration. The aim of the present study was to delineate the extent of the Fos expression as a marker of neuronal activation within the hypothalamic structures involved in food intake regulation after peripherally administered palmitoylated PrRP31 (palm-PrRP31) and to determine whether the anorexigenic effect of peripherally administered palm-PrRP31 influence the activity of hypocretin (HCRT) and oxytocin (OXY) neurons, i.e., the neuropeptides crucially involved in the regulation of energy homeostasis. The data confirmed an anorexigenic effect of palm-PrRP31 treatment (5mg/kg, s.c.) in mice. In the palm-PrRP31-treated animals, a significant increase in Fos expression was observed in the hypothalamic paraventricular (PVN), dorsomedial (DMN), and arcuate (Arc) nuclei and in the neurons of the nucleus of the solitary tract (NTS). Moreover, significant Fos expression was observed in the lateral hypothalamic area (LHA) HCRT neurons and PVN OXY neurons after palm-PrRP31 administration. The present findings may indicate that palm-PrRP31 may be involved in energy homeostasis via the activation of several hypothalamic structures. Fos activation of the hypothalamic OXY and HCRT neurons in the PVN and LHA emphasizes the importance of the areas mentioned in the central action of palm-PrRP31.

The paraventricular nucleus of the thalamus is differentially recruited by stimuli conditioned to the availability of cocaine versus palatable food.

The paraventricular nucleus of the thalamus (PVT) is not traditionally considered part of the brain addiction neurocircuitry but has received growing attention with regard to a role in the modulation of drug-seeking behavior. This study sought to establish the pattern of neural activation induced by a response-reinstating discriminative stimulus (SD ) conditioned to either cocaine (COC) or a conventional reinforcer using a palatable food substance, sweetened condensed milk (SCM). Male Wistar rats were trained to associate one SD (S+ ; COC or SCM availability) and a distinctly different SD (S- ; non-reward; i.e. the availability of saline or the absence of SCM). Following extinction of COC- and SCM-reinforced responding, rats were presented with the respective S+ or S- alone and tested for the reinstatement of reward seeking. The COC S+ and SCM S+ elicited identical reinstatement, whereas the non-reward S- was behaviorally ineffective. PVT sections were obtained following completion of the reinstatement tests and labeled for Fos. The number of Fos+ neurons was compared among rats that were presented with the COC S+ , SCM S+ or S- . Rats that were presented with the COC S+ exhibited a significant increase in Fos expression compared with rats that were presented with the S- . Moreover, Fos expression was significantly correlated with the number of reinstatement responses that were induced by the COC S+ . In contrast, the SCM S+ and S- produced identical increases in Fos expression, without behaviorally relevant correlations. The findings implicate the PVT as an important site that is selectively recruited during COC-seeking behavior.

Neuronal NOS Inhibitor and Conventional Antidepressant Drugs Attenuate Stress-induced Fos Expression in Overlapping Brain Regions

Recent evidence indicates that the administration of inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant-like effects in animal models such as the forced swimming test (FST). However, the neural circuits involved in these effects are not yet known. Therefore, this study investigated the expression of Fos protein, a marker of neuronal activity, in the brain of rats submitted to FST and treated with the preferential nNOS inhibitor, 7-nitroindazole (7-NI), or with classical antidepressant drugs (Venlafaxine and Fluoxetine). Male Wistar rats were submitted to a forced swimming pretest (PT) and, immediately after, started receiving a sequence of three ip injections (0, 5, and 23h after PT) of Fluoxetine (10mg/kg), Venlafaxine (10mg/kg), 7-NI (30mg/kg) or respective vehicles. One hour after the last drug injection the animals were submitted to the test session, when immobility time was recorded. After the FST they were sacrificed and had their brains removed and processed for Fos immunohistochemistry. Independent group of non-stressed animals received the same drug treatments, or no treatment (naïve). 7-NI, Venlafaxine or Fluoxetine reduced immobility time in the FST, an antidepressant-like effect. None of the treatments induce significant changes in Fos expression per se. However, swimming stress induced significant increases in Fos expression in the following brain regions: medial prefrontal cortex, nucleus accumbens, locus coeruleus, raphe nuclei, striatum, hypothalamic nucleus, periaqueductal grey, amygdala, habenula, paraventricular nucleus of hypothalamus, and bed nucleus of stria terminalis. This effect was attenuated by 7-NI, Venlafaxine or Fluoxetine. These results show that 7-NI produces similar behavioral and neuronal activation effects to those of typical antidepressants, suggesting that these drugs share common neurobiological substrates.

Fos expression in arousal and reward areas of the brain in grass rats following induced wakefulness

In the diurnal grass rat nocturnal voluntary wakefulness induces Fos expression in specific cellular populations of arousal and reward areas of the brain. Here, we evaluated whether involuntary wakefulness would result in similar patterns of Fos expression. We assessed this question using male grass rats that were sleep deprived for 6h by gentle stimulation (SD group), starting 2h before lights off (12:12 LD cycle). Then, we examined expression of Fos in cholinergic cells of the basal forebrain (BF), as well as in dopaminergic cells of the reward system, and compared these results to those obtained from an undisturbed control group. Different from previous results with grass rats that were voluntary awake, the BF of SD animals only showed a significant increase in Fos expression in non-cholinergic neurons of the medial septum (MS). These observations differ from reports for nocturnal rodents that are sleep deprived. Thus, our results show that voluntary and induced wakefulness have different effects on neural systems involved in wakefulness and reward, and that the effects of sleep deprivation are different across species. We also investigated whether other arousal promoting regions and circadian and stress related areas responded to sleep deprivation by changing the level of Fos expression. Among these areas, only the lateral hypothalamus (LH) and the ventro lateral preoptic area showed significant effects of sleep deprivation that dissipated after a 2h period of sleep recovery, as it was also the case for the non-cholinergic MS. In addition, we found that Fos expression in the LH was robustly associated with Fos expression in other arousal and reward areas of the brain. This is consistent with the view that the arousal system of the LH modulates neural activity of other arousal regions of the brain, as described for nocturnal rodents.

Brain–gut interactions between central vagal activation and abdominal surgery to influence gastric myenteric ganglia Fos expression in rats

We previously showed that medullary thyrotropin-releasing hormone (TRH) or the stable TRH agonist, RX-77368 administered intracisternally induces vagal-dependent activation of gastric myenteric neurons and prevents post surgery-induced delayed gastric emptying in rats. We investigated whether abdominal surgery alters intracisternal (ic) RX-77368 (50 ng)-induced gastric myenteric neuron activation. Under 10 min enflurane anesthesia, rats underwent an ic injection of saline or RX-77368 followed by a laparotomy and a 1-min cecal palpation, or no surgery and were euthanized 90 min later. Longitudinal muscle/myenteric plexus whole-mount preparations of gastric corpus and antrum were processed for immunohistochemical detection of Fos alone or double labeled with protein gene-product 9.5 (PGP 9.5) and vesicular acetylcholine transporter (VAChT). In the non surgery groups, ic RX-77368 induced a 17 fold increase in Fos-expression in both gastric antrum and corpus myenteric neurons compared to saline injected rats. PGP 9.5 ascertained the neuronal identity of myenteric cells expressing Fos. In the abdominal surgery groups, ic RX-77368 induced a significant increase in Fos-expression in both the corpus and antrum myenteric ganglia compared with ic saline injected rats which has no Fos in the gastric myenteric ganglia. However, the response was reduced by 73–78% compared with that induced by ic RX 77368 without surgery. Abundant VAChT positive nerve fibers were present around Fos positive neurons. These results indicate a bidirectional interaction between central vagal stimulation of gastric myenteric neurons and abdominal surgery. The modulation of gastric vagus-myenteric neuron activity could play an important role in the recovery phase of postoperative gastric ileus.

Differential respiratory control of the upper airway and diaphragm muscles induced by 5-HT1A receptor ligands

Serotonin (5-HT) has a role in respiratory function and dysfunction. Although 5-HT affects respiratory drive to both phrenic and cranial motoneurons, relatively little is known about the role of 5-HT receptor subtypes in the control of upper airway muscle (UAM) respiratory activity. Here, we performed central injections of 5-HT1A agonist (8-OHDPAT) or antagonist (WAY100635) in anesthetized rats and analyzed changes in the electromyographic activity of several UAM and other cardiorespiratory parameters. We also compared the pattern of Fos expression induced after central injection of a control solution or 8-OHDPAT. Results showed that 8-OHDPAT induced a robust increase in UAM activity, associated with either tachypnea under volatile anesthesia or bradypnea under liquid anesthesia. Injection of WAY100635 switched off UAM respiratory activity and led to bradypnea, suggesting a tonic excitatory role of endogenous 5-HT1A receptor activation. Co-injection of the agonist and the antagonist blocked the effects produced by each drug alone. Besides drug-induced changes in respiratory frequency, only slight increases in surface of diaphragm bursts were observed. Significant increases in Fos expression after 5-HT1A receptor activation were seen in the nucleus tractus solitarius, nucleus raphe pallidus, parapyramidal region, retrotrapezoid nucleus, lateral parabrachial, and Kölliker-Fuse nuclei. This restricted pattern of Fos expression likely identified the neural substrate responsible for the enhancement of UAM respiratory activity observed after 8-OHDPAT injection. These findings suggest an important role for the 5-HT1A receptors in the neural control of upper airway patency and may be relevant to counteract pharyngeal atonia during obstructive sleep apneas.

Effect of amniotic-fluid ingestion on vaginal–cervical-stimulation-induced Fos expression in female rats during estrus

Placental Opioid-Enhancing Factor (POEF) is a substance found in amniotic fluid (AF) that, when ingested, potentiates opioid-mediated, but not non-opioid-mediated, hypoalgesia. Vaginal–cervical stimulation (VCS) produces a stimulus-bound, partially opioid-mediated hypoalgesia that previous research has shown to be potentiated by AF ingestion. To understand the mechanism of opioid enhancement by POEF we investigated the pattern of neural activation after a bout of VCS that produced hypoalgesia, with and without co-administration of AF. Specifically, virgin Long–Evans rats showing vaginal estrus were handled briefly (control) or received VCS (75 g pressure, 1 min), in a pattern that approximated early parturition rather than copulation, using a spring-loaded glass-rod probe. Rats were given an orogastric infusion (0.25 ml) of either AF or 0.9% saline resulting in four groups (VCS or handling; AF or saline). Rats were perfused 90 min after treatment and tissue was processed by immunohistochemistry for Fos. The number of Fos-immunoreactive cells was counted in structures previously shown to express Fos in response to VCS (the medial preoptic area, MPOA; the ventrolateral portion of the ventromedial hypothalamic nucleus, vlVMH; the arcuate nucleus, ARC). We found that this pattern of VCS did not produce a significant increase in Fos expression in the MPOA and vlVMH unless it was paired with AF. VCS produced a significant increase in Fos in the ARC. The interaction of AF and VCS on Fos expression in the MPOA suggests that POEF may enhance vaginal–cervical sensory input at parturition to facilitate sensitization of the MPOA, and presumably facilitate maternal-behavior onset.

A sex comparison of the anatomy and function of the main olfactory bulb–medial amygdala projection in mice

We previously reported that some main olfactory bulb (MOB) mitral/tufted (M/T) cells send a direct projection to the “vomeronasal” amygdala in female mice and selectively respond to volatile male mouse urinary odors. We asked whether MOB M/T cells that project to the vomeronasal amygdala exist in male mice and whether there is a sexually dimorphic response of these neurons to volatile male urinary pheromones. Gonadectomized male and female mice received bilateral injections of the retrograde tracer, Cholera toxin-B (CTb) into the medial amygdala (Me), which is part of the vomeronasal amygdala. All subjects were then treated with estradiol benzoate and progesterone before being exposed to volatile male urinary odors whereupon they were sacrificed 90 min later. Sections of the MOB were immunostained for Fos protein and/or CTb. Male mice, like females, displayed a small population of MOB M/T cells that project to the Me. While the general localization of these cells was similar in the two sexes, there were statistically significant sex differences in the percentage of MOB M/T cells in the anterior and posterior medial segments of the MOB that were retrogradely labeled by CTb. Male urinary volatiles stimulated equivalent, significant increases in Fos expression by MOB M/T neurons projecting to the Me in the two sexes. By contrast, in the same mice exposure to male urinary volatiles stimulated a significant increase in Fos expression by mitral cells in the accessory olfactory bulb (AOB) only in female subjects. Thus any sexually dimorphic behavioral or neuroendocrine responses to male urinary volatiles likely depend on the differential processing of these odor inputs in the AOB and/or other downstream forebrain structures after their detection by the main olfactory system.

Effect of CFMTI, an allosteric metabotropic glutamate receptor 1 antagonist with antipsychotic activity, on Fos expression in regions of the brain related to schizophrenia

The main purpose of this study was to explore the sites and mechanisms of action of metabotropic glutamate receptor 1 (mGluR1) blockade for antipsychotic-like activity using a Fos mapping approach, with the intent of better understanding the similarities and differences between the pharmacological actions of mGluR1 antagonists and atypical antipsychotic drugs such as clozapine. Previously, we showed that an allosteric mGluR1 antagonist (negative allosteric modulator), 2-cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one (CFMTI), induces Fos expression in the nucleus accumbens and the medial prefrontal cortex (mPFC), but not in the dorsolateral striatum, similar to the action of clozapine. In the present study, the Fos expression profile of CFMTI was more extensively evaluated in various areas of the brain. CFMTI induced Fos expression mainly in glutamatergic neurons in the mPFC, in a manner similar to clozapine. A significant increase in Fos expression was also observed in the locous coeruleus, central amygdaloid nucleus, the bed nucleus of the stria terminalis and the primary somatosensory cortex, but not in the ventral tegmental area, dorsal raphe or lateral septum. Fos expression in orexin neurons in the lateral hypothalamic/perifornical area (LH/PFA) is known to be positively correlated with the weight gain liability of atypical antipsychotics. CFMTI did not increase Fos expression in orexin neurons in the LH/PFA, in contrast to clozapine, which does have weight gain liability. These results suggest that CFMTI has unique and shared actions on Fos expression in various regions of the brain compared with clozapine.

Nutritional status modulates behavioural and olfactory bulb Fos responses to isoamyl acetate or food odour in rats: roles of orexins and leptin

Food odours are major determinants for food choice, and their detection depends on nutritional status. The effects of different odour stimuli on both behavioural responses (locomotor activity and sniffing) and Fos induction in olfactory bulbs (OB) were studied in satiated or 48-h fasted rats. We focused on two odour stimuli: isoamyl acetate (ISO), as a neutral stimulus either unknown or familiar, and food pellet odour, that were presented to quiet rats during the light phase of the day. We found significant effects of nutritional status and odour stimulus on both behavioural and OB responses. The locomotor activity induced by odour stimuli was always more marked in fasted than in satiated rats, and food odour induced increased sniffing activity only in fasted rats. Fos expression was quantified in periglomerular, mitral and granular OB cell layers. As a new odour, ISO induced a significant increase in Fos expression in all OB layers, similar in fasted and satiated rats. Significant OB responses to familiar odours were only observed in fasted rats. Among the numerous peptides shown to vary after 48 h of fasting, we focused on orexins (for which immunoreactive fibres are present in the OB) and leptin, as a peripheral hormone linked to adiposity, and tested their effects of food odour. The administration of orexin A in satiated animals partially mimicked fasting, since food odour increased OB Fos responses, but did not induce sniffing. The treatment of fasted animals with either an orexin receptors antagonist (ACT-078573) or leptin significantly decreased both locomotor activity, time spent sniffing food odour and OB Fos induction in all cell layers, thus mimicking a satiated status. We conclude that orexins and leptin are some of the factors that can modify behavioural and OB Fos responses to a familiar food odour.

The impact of early environmental rearing condition on the discriminative stimulus effects and Fos expression induced by cocaine in adult male and female rats.

A number of environmental manipulations, including maternal separation (MS), have been shown to alter behavioral responses to drugs of abuse. This study assessed if MS affected the stimulus and Fos-inducing effects of cocaine. In experiment 1, male and female Sprague-Dawley rats were exposed to brief maternal separations (BMS), long maternal separations (LMS), or animal facility rearing (AFR) and then trained as adults to discriminate cocaine (10 mg/kg, intraperitoneally) from saline. Following training, generalization tests to novel doses of cocaine and other dopaminergic compounds were performed. Assessments of variations in training dose pretreatment times were also made. In experiment 2, male and female rats exposed to MS conditions were administered cocaine or saline for 14 days, and Fos expression in the mesolimbic system was measured. In males, BMS retarded the acquisition of the cocaine discrimination. Generalization to novel doses of cocaine did not differ among rearing conditions, but the training dose cue lasted longer in LMS. Distinct generalization and ED(50) profiles were found between male rearing conditions for all dopamine compounds. While BMS females had higher cocaine ED(50) estimates, no other differences were found in females. LMS males and females, as well as AFR females, had significant increases in Fos expression after cocaine in a region-specific manner. No differences were found with other rearing groups. Early environmental variables altered the stimulus effects (in a sex-dependent manner) as well as the neuronal responsiveness to cocaine, which may be mediated by the dopamine system.

Fos-like immunoreactivity in rat dorsal raphe nuclei induced by alkaloid extract of Mitragyna speciosa

Mitragyna speciosa (MS) has been traditionally used for medicinal purposes especially in southern Thailand. Previously, an alkaloid extract of this plant was demonstrated to mediate antinociception, partly, through the descending serotonergic system. The present study investigated the stimulatory effect of the MS extract on the dorsal raphe nucleus and its antidepressant-like activity. The MS extract containing approximately 60% mitragynine as a major indole alkaloid was used to treat the animals. The stimulatory effect of the MS extract was determined by detecting the expression of the immediate early gene, cfos, in the dorsal raphe nucleus of male Wistar rats. The immunohistochemistry was used to detect Fos protein, the protein product of cfos gene. The present data show that a significant increase in Fos expression was observed following long-term administration of the MS extract (40 mg/kg) for 60 consecutive days. In addition, the antidepressant-like activity of the MS extract was determined by using the forced swimming test (FST) in male mice. The results show that a single injection (either 60 or 90 mg/kg doses) significantly decreased immobility time in the FST. These findings indicate that the MS extract has a stimulatory effect on the dorsal raphe nucleus and an antidepressant-like activity. Stimulation of this brain area has been known to cause antinociception. These findings suggest that the MS extract might produce antinociceptive and/or antidepressive actions partly through activation of the dorsal raphe nucleus. Moreover, the dorsal raphe nucleus may be one of site of MS action in the central nervous system.

Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is critical for the adaptation and survival of animals upon exposure to stressful stimuli, and data suggest that endocannabinoid (eCB) signaling modulates neuroendocrine function. We have explored the role of eCB signaling in the modulation of stress-induced HPA axis activation. Administration of the CB1 receptor antagonist/inverse agonist SR141716 (0.01, 0.1, 1, and 5 mg/kg, i.p.) to male mice produced a small, dose-dependent increase in the serum corticosterone (CORT) concentration. Despite this effect, the highest dose of SR141716 did not significantly increase neuronal activity within the paraventricular nucleus of the hypothalamus, as measured by the induction of Fos protein. Similarly, exposure of mice to 30 min of restraint increased serum CORT concentrations, but did not produce a consistent, statistically significant increase in Fos expression within the PVN. However, pretreatment of mice with SR141716 before restraint stress robustly potentiated restraint-induced CORT release and Fos expression within the PVN. Pretreatment of mice with either the CB1 receptor agonist CP55940, the eCB transport inhibitor AM404, or the fatty acid amide hydrolase inhibitor URB597 significantly decreased or eliminated restraint-induced CORT release. Upon exposure to acute restraint, hypothalamic 2-arachidonylglycerol content was reduced compared with the control value; however, after 5 d of restraint exposure (which resulted in an attenuated CORT response), the hypothalamic 2-arachidonylglycerol content was increased compared with the control value. These data indicate that eCB signaling negatively modulates HPA axis function in a context-dependent manner and suggest that pharmacological augmentation of eCB signaling could serve as a novel approach to the treatment of anxiety-related disorders.

Mapping the Neural Substrates Involved in Maternal Responsiveness and Lamb Olfactory Memory in Parturient Ewes Using Fos Imaging.

In sheep, recognition of the familiar lamb by the mother depends on the learning of its olfactory signature after parturition. The authors quantified Fos changes in order to identify brain regions activated during lamb odor memory formation. Brain activation was compared with those measured in anosmic ewes displaying maternal behavior but not individual lamb recognition. In intact ewes, parturition induced significant increase in Fos expression in olfactory cortical regions and in cortical amygdala, whereas in anosmic mothers, Fos expression was very low. In contrast, no difference was observed between intact and anosmic ewes in hypothalamic areas and medial amygdala, suggesting a differentiation between the neural network controlling maternal responsiveness and that involved in olfactory lamb memory.

The effects of dentate granule cell destruction on behavioral activity and Fos protein expression induced by systemic MDMA in rats

In this study, we examined the effect of the s.c. administration of (±) 3,4-methylenedioxymethamphetamine (MDMA) or saline on locomotor activity and Fos expression following the bilateral destruction of hippocampal dentate granule cells by colchicine in rats. The lesioned animals, when administered s.c. saline, showed a significantly greater increase in locomotor activity compared to the intact animals, and revealed a marginally significant level of increased locomotor activity compared to the sham-lesioned animals. In addition, when the lesioned animals were given s.c. saline or MDMA, there was a significant increase in Fos expression in the nucleus accumbens core, but not in the medial prefrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, piriform cortex, dorsal striatum, or nucleus accumbens shell, compared to the intact and sham-lesioned animals. Overall, these results suggest that the nucleus accumbens core may be involved in the enhancement of locomotor activity induced by the injection of saline alone (stress loading) or MDMA following bilateral destruction of hippocampal dentate granule cells by colchicine.

Effects of morphine and morphine withdrawal on brainstem neurons innervating hypothalamic nuclei that control the pituitary-adrenocortical axis in rats.

Different data support a role for brainstem noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) in the control of hypothalamus - pituitary - adrenocortical (HPA) axis. However, little is known regarding the functional adaptive changes of noradrenergic afferent innervating the PVN and supraoptic nucleus (SON) during chronic opioid exposure and upon morphine withdrawal. Here we have studied the expression of Fos after administration of morphine and during morphine withdrawal in the rat hypothalamic PVN and SON. Fos production was also studied in brainstem regions that innervate hypothalamic nuclei: the nucleus of solitary tract (NTS - A2) and the ventrolateral medulla (VLM - A1) and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurons during morphine withdrawal. Male rats were implanted with s.c. placebo or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received an injection of saline i.p., morphine i.p., saline s.c. or naloxone s.c. Acute morphine administration produced an increase in Fos expression at hypothalamic nuclei and in the brainstem regions, and tolerance developed towards this effect. Precipitated morphine withdrawal induced marked Fos immunoreactivity within the PVN and SON. Concomitantly, numerous neurons in the brainstem were stimulated by morphine withdrawal. Moreover, catecholaminergic-positive neurons in the brainstem showed a significant increase in Fos expression in response to morphine withdrawal. These findings demonstrate that chronic activation of opioid receptors results in altered patterns of immediate-early genes (IEG) expression in the PVN and SON, which occurs concurrently with an increased activity of their inputs from the brainstem.

Intrapericardial Procaine Affects Volume Expansion-Induced Fos Immunoreactivity in Unanesthetized Rats

Acute volume expansion is associated with a specific pattern of Fos expression and the goal of the present study was to evaluate the contribution of cardiac receptors to this response. Adult male rats were instrumented with pericardial catheters introduced at the level of the thymus. Rats were also catheterized for measuring blood pressure, heart rate, central venous pressure, and intravenous infusion. Each rat received a 200-μl intrapericardial (i.p.c) injection of 2% procaine or 0.9% NaCl. Rats were then volume expanded with isotonic saline (10% body weight in 10 min) or given a control infusion (0.01 ml/min for 10 min). Ninety minutes after the start of the infusion, the rats were anesthetized and perfused transcardially. Their brains were sectioned and processed for Fos, dopamine-β-hydroxylase, and oxytocin immunocytochemistry. Volume expansion plus i.p.c. saline produced a significant increase in Fos expression in the nucleus of the solitary tract, the ventrolateral medulla, the area postrema, the locus coeruleus, the paraventricular nucleus of the hypothalamus, the perinuclear zone of the supraoptic nucleus, and oxytocin neurons in the supraoptic nucleus. The i.p.c. procaine significantly blocked Fos expression produced by the volume expansion in the all of the regions examined except for the area postrema and the SON oxytocin neurons.