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Adrian J Dunn

Publications and source records attributed to Adrian J Dunn.

At least 19 recordsLinked to original sources
PubMed2006

Reduced ingestion of sweetened milk induced by interleukin-1 and lipopolysaccharide is associated with induction of cyclooxygenase-2 in brain endothelia.

UNLABELLED: Previous studies have shown that interleukin-1 (IL-1) and lipopolysaccharide (LPS) administration to animals induces behavioral changes, including a reduction in feeding. These effects of IL-1 and LPS have been shown to be sensitive to inhibitors of cyclooxygenase (COX). OBJECTIVES: To determine the relationships between induction of COX-2 in the brain with IL-1beta- and LPS-induced changes in body temperature, plasma corticosterone and feeding. METHODS: Mice were injected with intraperitoneal doses of IL-1beta and LPS that decreased feeding. The induction of COX-2 was studied immunocytochemically in the brain, in parallel with core body temperature, the drinking of sweetened milk, and plasma concentrations of corticosterone. RESULTS: COX-2 immunoreactivity (ir) was sparse in the brains of the untreated mice, but IL-1beta and LPS both increased its expression. This COX-2 induction appeared to be confined to blood vessels, and was not markedly region specific. Induction was evident 30 min after IL-1 or LPS, and was greater at 90 than at 30 min. COX-2-ir in the parenchyma did not change significantly. Thus induction of COX-2 occurred in brain endothelia in parallel with the reduction in feeding. This is consistent with the previously determined sensitivity of IL-1-induced changes in feeding to selective COX-2 inhibitors, and the responses to IL-1 in COX-2-deficient mice. The time courses of the IL-1- and LPS-induced increases in plasma corticosterone paralleled those in the reduction in milk drinking, however, the changes in body temperature appeared later. CONCLUSIONS: Endothelial COX-2 may be involved in IL-1- and LPS-induced decreases in milk drinking, and possibly in the HPA axis activation. The decreased milk drinking may occur when IL-1 and LPS bind to receptors on brain endothelial cells subsequently inducing COX-2 and the production of prostanoids which elicit the reductions in milk drinking. Thus the behavioral effects of peripherally administered IL-1 and LPS appear to be mediated by multiple mechanisms, including endothelial COX-2, and vagal afferents.

Animals↗
PubMed2006

Effect of subdiaphragmatic vagotomy on the noradrenergic and HPA axis activation induced by intraperitoneal interleukin-1 administration in rats.

The vagus nerve is thought to participate in signal transduction from the immune system to the CNS. The role of the vagus in the physiological, behavioral and neurochemical responses to intraperitoneally (ip) injected interleukin-1beta (IL-1beta) was studied using awake subdiaphragmatically vagotomized rats. The rats were injected ip with saline and IL-1beta (1 microg/rat) in random order. For the next 2-4 h, they were monitored for locomotor activity, body temperature via abdominally implanted telethermometers, hypothalamic norepinephrine (NE) secretion using in vivo microdialysis and blood sampled via intravenous catheters to determine concentrations of ACTH and corticosterone to assess hypothalamo-pituitary-adrenocortical (HPA) axis activation. Saline injections were followed by transient increases in locomotor activity, body temperature, dialysate NE and plasma concentrations of ACTH and corticosterone. These responses were not significantly altered by vagotomy. IL-1beta injections resulted in short-lived increases in shivering and longer decreases in locomotor activity, as well as a delayed modest fever. IL-1beta also induced prolonged elevations of hypothalamic microdialysate NE, as well as plasma ACTH and corticosterone. Similar responses were observed regardless of the order of the saline and IL-1beta injections. Subdiaphragmatic vagotomy prevented the IL-1-induced increases in body temperature and the increase in dialysate NE, and markedly attenuated the increases in plasma ACTH and corticosterone. The results indicate close temporal relationships between the apparent release of NE and the increase in body temperature and the HPA activation. This together with the effects of vagotomy suggests that the activation of NE in turn increases body temperature and activates the HPA axis. However, because IL-1beta induces a limited HPA activation in subdiaphragmatically vagotomized rats, the vagus nerve does not appear to be the only route by which ip IL-1beta can activate the HPA axis. It is suggested that IL-1beta-induced vagal activation of hypothalamic NE is the major mechanism of HPA activation at low doses of IL-1beta. However, IL-1beta can also exert direct effects on IL-1 receptors on cerebral blood vessels, activating cyclooxygenases and hence synthesis of prostaglandins which in turn can affect body temperature, behavior and HPA axis activation.

Adrenocorticotropic Hormone↗
PubMed2006

Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice.

Interleukin-6 (IL-6) has been implicated in behavioral responses associated with inflammation, sickness behavior and various nervous system disorders. We studied a range of different behaviors in IL-6-knockout (IL-6ko) and wild-type (WT) male mice. No significant differences were observed in ambulatory, exploratory, and stereotypic activities in home or novel cages, in an open field (OF), in the multicompartment chamber (MCC), or in the elevated plus-maze (EPM). IL-6ko mice shed fewer fecal boli than WT mice in the OF, in novel cages and in the MCC although this effect was not statistically significant in the OF. In novel cages, intraperitoneal (i.p.) injection of IL-6 (1 microg) depressed ambulatory activity slightly more in IL-6ko than in WT mice. Restraint and interleukin-1beta (IL-1beta, 100 ng i.p.) decreased exploration of mice in the MCC and EPM, but there was no indication of altered sensitivity in IL-6ko mice. No significant differences were detected in the tail suspension and the Porsolt forced swim tests. IL-1beta and lipopolysaccharide (LPS 1 microg i.p.) injection depressed sweetened milk and solid food intake similarly in IL-6ko and WT mice, but IL-6 had no effect, suggesting that IL-6 is not involved in these effects of IL-1 or LPS. However, IL-1beta and LPS depressed body weight more in WT than in IL-6ko mice. Plasma corticosterone and basal concentrations of catecholamines, indoleamines and their metabolites in several brain regions were similar. The responses in these measures to IL-1beta and LPS were also similar, except that there were no significant changes in tryptophan and serotonin metabolism in IL-6ko mice. This may reflect a role for IL-6 in the tryptophan and serotonin responses to IL-1 and LPS. It is concluded that the lack of IL-6 is not associated with substantial alterations in several different mouse behaviors, and in the responses to restraint, IL-1beta, IL-6 and LPS.

Adrenocorticotropic Hormone↗
PubMed2005

Relationships among the behavioral, noradrenergic, and pituitary-adrenal responses to interleukin-1 and the effects of indomethacin.

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.

Adrenocorticotropic Hormone↗
PubMed2005

Physiological and behavioral responses to interleukin-1beta and LPS in vagotomized mice.

It is well established that peripheral administration of interleukin-1 (IL-1) and lipopolysaccharide (LPS) can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, alter brain catecholamine and indoleamine metabolism, and affect behavior. However, the mechanisms of these effects are not fully understood. Stimulation of afferents of the vagus nerve has been implicated in the induction of Fos in the brain, changes in body temperature, brain norepinephrine, and some behavioral responses. In the present study, the IL-1beta- and LPS-induced changes in certain behaviors, HPA axis activation, and catecholamine and indoleamine metabolism were studied in mice following subdiaphragmatic vagotomy. IL-1beta and LPS induced the expected decreases in sweetened milk, food intake, and locomotor activity, and the responses to IL-1beta, but not LPS, were slightly attenuated in vagotomized mice. Subdiaphragmatic vagotomy also attenuated the IL-1beta- and LPS-induced increases in plasma ACTH and corticosterone, but the attenuations of the responses to IL-1beta were only marginally significant. There were also slight reductions in the responses in catecholamine and serotonin metabolism, and the increases in brain tryptophan in several brain regions. These results indicate that the vagus nerve is not the major pathway by which abdominal IL-1beta and LPS effect behavioral, HPA and brain catecholamine and indoleamine responses in the mouse. These results resemble those we observed in subdiaphragmatically vagotomized rats, but in that species the subdiaphragmatic vagotomy markedly attenuated the ACTH and corticosterone responses, and prevented the hypothalamic noradrenergic activation, as well as the fever. Overall the results indicate that the various responses to peripheral IL-1 and LPS involve multiple mechanisms including vagal afferents, and that there are species differences in the relative importance of the various mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2005

Fast 1H-13C correlation data for use in automatic structure confirmation of small organic compounds.

A method of speeding up the acquisition of 1H-13C correlation data has been developed. It is applicable in situations where the experiment time is determined by the need to sample the second dimension adequately rather than by signal-to-noise ratio requirements. Two spectra with different, reduced, 13C sweep widths are measured, time being saved by reducing the number of increments in line with the reduction in the sweep width. Rules are presented for the selection of the two reduced sweep widths so that the correct 13C chemical shifts can be easily and unambiguously calculated. The benefits and limitations of this approach, in the context of the structure confirmation of small (MW < or = 450) organic compounds, is discussed. The use of a third spectrum to resolve problems that may be encountered when proton signals overlap is demonstrated.

Journal Article↗
PubMed2005

Mechanisms and significance of the increased brain uptake of tryptophan.

Changes in brain tryptophan concentrations may affect the synthesis of brain serotonin (5-hydroxytryptamine, 5-HT). Concentrations of tryptophan are regulated more than those of any other amino acid. Such stimuli as acute stress, carbohydrate ingestion, and treatment with various drugs increase the brain content of tryptophan. Treatment of rats and mice with interleukin-1 (IL-1), interleukin-6 (IL-6), lipopolysaccharide (LPS), and beta-adrenoceptor agonists, as well as a variety of stressors, such as footshock and restraint, all increase brain concentrations of tryptophan. The peak effect following both acute stress and beta-adrenoceptor agonist administration occurs within 30-60 min, whereas the peak effect following LPS and the cytokines occurs much later at around 4-8 h. Experiments using the ganglionic blocker chlorisondamine, and beta-adrenoceptor antagonists suggest that the sympathetic nervous system plays an important role in the modulation of brain tryptophan concentrations. The mechanisms involved in the increases observed in brain tryptophan are discussed, as well as their possible biological significance.

Animals↗
PubMed2005

Cytokines as mediators of depression: what can we learn from animal studies?

It has recently been postulated that cytokines may cause depressive illness in man. This hypothesis is based on the following observations: 1. Treatment of patients with cytokines can produce symptoms of depression; 2. Activation of the immune system is observed in many depressed patients; 3. Depression occurs more frequently in those with medical disorders associated with immune dysfunction; 4. Activation of the immune system, and administration of endotoxin (LPS) or interleukin-1 (IL-1) to animals induces sickness behavior, which resembles depression, and chronic treatment with antidepressants has been shown to inhibit sickness behavior induced by LPS; 5. Several cytokines can activate the hypothalamo-pituitary-adrenocortical axis (HPAA), which is commonly activated in depressed patients; 6. Some cytokines activates cerebral noradrenergic systems, also commonly observed in depressed patients; 7. Some cytokines activate brain serotonergic systems, which have been implicated in major depressive illness and its treatment. The evidence for each of these tenets is reviewed and evaluated along with the effects of cytokines in classical animal tests of depression. Although certain sickness behaviors resemble the symptoms of depression, they are not identical and each has distinct features. Thus the value of sickness behavior as an animal model of major depressive disorder is limited, so that care should be taken in extrapolating results from the model to the human disorder. Nevertheless, the model may provide insight into the etiology and the mechanisms underlying some symptoms of major depressive disorder. It is concluded that immune activation and cytokines may be involved in depressive symptoms in some patients. However, cytokines do not appear to be essential mediators of depressive illness.

Animals↗
PubMed2005

Potential role for nonesterified fatty acids in beta-adrenoceptor-induced increases in brain tryptophan.

We tested the hypothesis that beta2- and beta3-adrenergic receptor-mediated increases in brain tryptophan are due to the liberation of fatty acids, which in turn displace tryptophan from its albumin-binding site and thus facilitate its entry into the brain. Male CD-1 mice were injected with subtype-selective beta-adrenergic agonists 1h before brain samples were collected for analysis of tryptophan content by HPLC with electrochemical detection, and blood samples were collected for analysis of total and free tryptophan and nonesterified fatty acid (NEFA) concentrations. The beta2-selective agonist, clenbuterol (0.1 mg/kg), increased concentrations of tryptophan in all brain regions studied and decreased plasma total tryptophan, but had no effect on plasma free tryptophan or NEFAs. The beta3-selective agonists, BRL 37344 (0.2 mg/kg) or CL 316243 (0.01 mg/kg), increased brain tryptophan, plasma NEFAs and free tryptophan. Pretreatment with nicotinic acid (500 mg/kg), an inhibitor of lipolysis, almost completely prevented the increase in plasma free tryptophan and NEFAs, and attenuated the increase in brain tryptophan induced by CL 316243. These results suggest that beta2- and beta3-adrenergic agonists increase brain tryptophan by a mechanism other than the liberation of NEFAs. Nonetheless, beta3-adrenergic agonists appear to increase brain tryptophan by a mechanism that may depend partially on elevations of plasma NEFAs.

Adrenergic beta-2 Receptor Agonists↗
PubMed2005

Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice.

Male CD-1 mice were administered interleukin-1beta (IL-1beta) and bacterial endotoxin (lipopolysaccharide, LPS) and subsequently tested in the tail suspension test (TST), the Porsolt forced swim test (FST), and in the open field. IL-1beta (100, 300 and 1000 ng/mouse) injected intraperitoneally (i.p.) 90 min before the test induced a dose-dependent increase in the time spent immobile in the TST and the time spent floating in the FST. These responses were statistically significant only at the higher doses of IL-1beta (300 and 1000 ng). Nevertheless, all three doses of IL-1beta significantly decreased line crossings and rears in the open field and depressed food intake and body weight. Very similar effects were induced by LPS. Doses of 1 and 5 mug i.p. increased immobility time in the TST and floating time in the FST, but the same doses strongly depressed locomotor activity and body weight. These results indicate that both IL-1beta and LPS can induce depression-like effects in the TST and the FST. However, the doses necessary to induce these changes reduced feeding and activity in an open field, so that the effects observed in the FST and TST could be attributed to a general reduction in locomotor activity. Thus the results obtained in these two animal tests commonly used to test antidepressant properties do not provide strong support for an IL-1 hypothesis of depression.

Animals↗
PubMed2004

Increased insulin is not required for beta2-adrenoceptor-induced increases in mouse brain tryptophan.

The current study tested the hypothesis that beta(2)-adrenoceptor-mediated increases in brain tryptophan are caused by increased insulin secretion. Male mice were treated with streptozotocin (40 mg/kg) for 5 days to induce experimental diabetes. Control and diabetic mice were treated with the beta(2)-adrenoceptor agonist, clenbuterol (0.1 mg/kg), 1 h before selected brain regions were dissected for analysis by high performance liquid chromatography (HPLC) with electrochemical detection for tryptophan content, and plasma was collected for analysis of total and free tryptophan and glucose concentrations. Clenbuterol increased brain tryptophan and plasma glucose and decreased plasma total tryptophan but did not alter plasma free tryptophan. There were no significant differences in brain or plasma tryptophan between control and streptozotocin-treated mice. In a separate experiment, pretreatment of the mice with an insulin antibody did not prevent the clenbuterol-induced increases in brain tryptophan. These results suggest that beta(2)-adrenoceptor agonists increase brain tryptophan by a mechanism that does not involve changes in insulin.

Adrenergic beta-2 Receptor Agonists↗
PubMed2004

A cytokine-based neuroimmunologic mechanism of cancer-related symptoms.

While many of the multiple symptoms that cancer patients have are due to the disease, it is increasingly recognized that pain, fatigue, sleep disturbance, cognitive dysfunction and affective symptoms are treatment related, and may lead to treatment delays or premature treatment termination. This symptom burden, a subjective counterpart of tumor burden, causes significant distress. Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients. Accordingly, we propose that cancer-related symptom clusters share common cytokine-based neuroimmunologic mechanisms. In this review, we provide evidence from clinical and animal studies that correlate the altered cytokine profile with cancer-related symptoms. We also propose that the expression of coexisting symptoms is linked to the deregulated activity of nuclear factor-kappa B, the transcription factor responsible for the production of cytokines and mediators of the inflammatory responses due to cancer and/or cancer treatment. These concepts open exciting new avenues for translational research in the pathophysiology and treatment of cancer-related symptoms.

Cytokines↗
PubMed2003

Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms.

BACKGROUND: Cancers and cancer treatments produce multiple symptoms that collectively cause a symptom burden for patients. These symptoms include pain, wasting, fatigue, cognitive impairment, anxiety, and depression, many of which co-occur. There is growing recognition that at least some of these symptoms may share common biologic mechanisms. METHODS: In November 2001, basic and clinical scientists met to consider evidence for a cytokine-immunologic model of symptom expression along with directions for future research. RESULTS: The characteristics of cytokine-induced sickness behavior in animal models have much in common with those of symptomatic cancer patients. Sickness behavior refers to a set of physiologic and behavioral responses observed in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines. In some cases, these responses can be prevented by cytokine antagonists. A combination of animal and human research suggests that several cancer-related symptoms may involve the actions of proinflammatory cytokines. CONCLUSIONS: Based on the similarities between cancer symptoms and sickness behavior, the authors discussed approaches to further test the implications of the relationship between inflammatory cytokines and symptoms for both symptom treatment and symptom prevention.

Animals↗
PubMed2003

Activation of beta2- and beta3-adrenergic receptors increases brain tryptophan.

Brain tryptophan concentrations are increased by various stressful treatments, an effect that can be prevented by beta-adrenoceptor antagonists. This study aimed to determine the beta-adrenergic subtype responsible for the tryptophan response. Male CD-1 mice received intraperitoneal injections of nonselective and subtype-selective beta-adrenergic antagonists 20 min before subtype-selective beta-agonists. Selected brain regions were dissected for analysis of tryptophan content by high-performance liquid chromatography with electrochemical detection. The beta(2)-selective agonist clenbuterol (0.3 mg/kg) induced increases in brain tryptophan that reached a peak ( approximately 60%) 1 h following injection and small but statistically significant increases ( approximately 20%) in 5-hydroxyindoleacetic acid: serotonin ratios 2 h following injection. The beta(1)-selective agonist dobutamine (10 mg/kg) produced less robust increases ( approximately 40%) in brain tryptophan, whereas the beta(3)-selective agonists BRL 37344 (0.2 mg/kg (+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino)propyl] phenoxy]acetic acid sodium)) and CL 316243 [0.1 mg/kg disodium 5-[(2R)-2-([(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino)propyl]-1,3-benzodioxole-2,2-dicarboxylate)] resulted in larger increases (80 to 100%). Pretreatment with the beta(2)-selective antagonist ICI 118551 (0.5 mg/kg (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxyl]-3-[(1-methylethyl)amino]-2-butanol) attenuated the increases in tryptophan induced by both clenbuterol (0.1 mg/kg) and dobutamine (10 mg/kg). Pretreatment with the beta(1/2)-selective antagonist propranolol (2.5 mg/kg), the beta(3)-selective antagonist SR 59230A [1.5, 2.5, 5, or 20 mg/kg (3-(2-ethylphenoxy)-1[1S)-1,2,3,4-tertahydronaphth-1-yl-amino]-(2S)-2-propanol oxalate)], or ICI 118551 (0.5 mg/kg) did not prevent the BRL 37344-induced increase in brain tryptophan, whereas the beta(1/2/3)-antagonist bupranolol (10 mg/kg) attenuated it. CL 316243 had no effect on brain tryptophan in beta(3)-receptor knockout mice, whereas clenbuterol increased brain tryptophan, indicating that beta-adrenergic modulation of brain tryptophan occurs in the absence of beta(3)-receptors. We conclude that activation of either beta(2)- or beta(3)-adrenergic receptors, but not beta(1)-adrenergic receptors, increases mouse brain tryptophan content.

Adrenergic beta-2 Receptor Agonists↗
PubMed2003

HPA axis activation and neurochemical responses to bacterial translocation from the gastrointestinal tract.

Stress can cause migration of indigenous bacterial flora from the gut to the peritoneum, a phenomenon known as bacterial translocation. Destruction of the cell walls of gram-negative bacteria can result in the production of endotoxin (lipopolysaccharide, LPS), which is the likely cause of sepsis. Exogenously administered LPS can activate the hypothalamo-pituitary-adrenal (HPA) axis as well as brain noradrenergic and indoleaminergic systems. Thus, it is possible that activations of these systems associated with laboratory stressors in rats and mice could be attributed to bacterial translocation and LPS production. To test this hypothesis we conducted experiments on the time course of bacterial translocation in response to restraint in mice, while measuring HPA and neurochemical responses. These experiments failed to show good correlations between the occurrence of bacterial translocation and HPA and neurochemical activations, suggesting that the later responses were not linked to bacterial translocation. This conclusion was supported by the observation of normal neurochemical responses to restraint in germ-free mice. In further experiments, translocation of Salmonella typhimurium, a bacterium that readily translocates in unstressed animals, was associated with HPA activation and noradrenergic and indoleaminergic responses, indicating that bacterial translocation can indeed activate the HPA axis and brain amines. However, the above experiments suggest that this is not the mechanism by which restraint activates these systems.

Animals↗
PubMed2002

Hippocampal noradrenergic responses to CRF injected into the locus coeruleus of unanesthetized rats.

Intracerebral administration of corticotropin-releasing factor (CRF) activates cerebral noradrenergic neurons. Direct infusion of CRF into the locus coeruleus (LC) increases norepinephrine (NE) release in the cortex and hippocampus as assessed by in vivo microdialysis. In a recent study using in vivo chronoamperometry in anesthetized rats, CRF injected into the LC increased apparent NE release in the hippocampus, but did so after a significant delay, much longer than observed following infusion of glutamate into the same site. Because this delay may have been an artifact of the urethane anesthesia, we developed a method for chronoamperometric recording from the hippocampus of unanesthetized rats. CRF infusion into the LC of such animals induced an increase in the apparent release of hippocampal NE after a mean delay of about 7 min, reached a peak around 16 min after CRF, and dissipated within 30 min. Thus the response closely resembled that previously reported in urethane-anesthetized rats. As in anesthetized rats, glutamate infused into the same site resulted in a much more rapid response (starting within 1 min and with a peak around 7 min). These results suggest that the urethane anesthesia does not substantially alter hippocampal NE release following infusion of CRF into the LC, and that the relatively long delay in the response is not an artifact of the anesthesia. The large differences in the responses to glutamate and CRF suggest that the effects of CRF are not exerted directly on receptors on LC neurons, and more likely reflect indirect actions on other cells in this region.

Animals↗
PubMed2002

Effects of interleukin-1beta on food-maintained behavior in the mouse.

The present studies compared the effect of parenteral administration of the proinflammatory cytokine interleukin-1beta (IL-1beta) on food-seeking behavior under various conditions. IL-1beta (100 ng/mouse) decreased home cage consumption of sweetened milk to a greater extent in ad libitum fed mice than in mice that were food-restricted to maintain 85-90% of their free-feeding body weight. When operant responding for milk was maintained under a fixed-ratio 10 response (FR10) schedule of milk delivery, IL-1beta (30-300 ng/mouse) significantly decreased milk-maintained responding in mice fed ad libitum, but not in food-restricted mice. When food-restricted mice were trained under either an FR4 or FR32 response schedule of milk delivery, IL-1beta (100-300 ng/mouse) produced significant decreases in FR32, but not in FR4 responding. When responding was maintained under a progressive-ratio 10 response (PR10) schedule of milk delivery, IL-1beta (30-300 ng/mouse) dose-dependently decreased breaking points. These results indicate that the effects of IL-1beta on food-maintained behavior depend on both the level of motivation (as assessed by food restriction) and on the response cost for the milk (as assessed by ratio requirement). These findings suggest that motivational factors may be capable of attenuating some of the behavioral effects of these agents.

Animals↗