Physiology of drinking elicited by eating.

Notes that much of normal drinking occurs around mealtime and that little is known about the physiological mechanisms involved, despite the identification of neurological substrates and physiological mechanisms for drinking in response to homeostatic deficit. The present author discusses the course of ingested food along the gastrointestinal tract, where food elicits a neuroendocrine cascade of events with the potential for mobilizing drinking. This perspective helps to identify histamine, and perhaps insulin and serotonin, as serving vagally mediated mechanisms that can elicit drinking around mealtime to preclude homeostatic imbalance. The experimental study of how normal drinking behavior ensures homeostasis by precluding homeostatic imbalance has the advantage of promising to enrich, rather than to damage, the status of homeostasis as a guiding principle for understanding the neurobiology of behavior. The concept would be enriched because it would become clear that cognitive functions such as learning, remembering, and planning one's behavior at times guarantee homeostasis and therefore prevent the necessity of a rapid behavioral response to repair the physiological emergency of a homeostatic deficit. (3? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preabsorptive pregastric vagally mediated histaminergic component of drinking elicited by eating in the rat.

Preabsorptive stimulation by food was confined to the pregastric (oropharynx and esophagus) segment of the gastrointestinal tract by having 40 male Sprague-Dawley rats sham-feed liquid food which then drained out a gastric cannula. This procedure provided a paradigm for studying the effect of preabsorptive pregastric food-contingent stimulation on drinking behavior. Sham feeding elicited drinking that was (a) attenuated by complete bilateral subdiaphragmatic vagotomy (with hepatic branch intact), (b) attenuated by peripheral cholinergic blockade with atropine methyl nitrate (0.25 mg/kg, ip), and (c) abolished by combined antagonism of H? and H? histamine receptors with the use of ip dexbrompheniramine (1 mg/kg) and cimetidine (16 mg/kg). Results provide evidence for a preabsorptive pregastric vagally medicated histaminergic component of drinking elicited by eating in the rat. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attack, eating, drinking, and gnawing elicited by electrical stimulation of rat mesencephalon and pons.

Conducted a study with 108 Long-Evans male rats. Eating, drinking, and gnawing were electrically elicited from the rat mesencephalon in the vicinity of the lateral branch of the descending medial forebrain bundle, but attack was evoked from the dorsomedial tegmentum adjacent to the central gray. The effective zones continued further caudally to the dorsal posterior pons. Unlike hypothalamically elicited behavior, eating, drinking, and gnawing often persisted 5-40 sec after termination of stimulation. Vocalization and escape activity were obtained principally from the vicinity of central pain pathways originating from the anterolateral cord. Other electrodes produced eating, drinking, gnawing, and grooming, which began only after termination of stimulation. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Histamine H3 receptor desensitization in the guinea-pig ileum

Histamine H3 receptor ligands are usually tested in guinea-pig intestine preparations. A possible desensitization of agonist-induced twitch inhibition was studied in longitudinal muscle-myenteric plexus from ileal segments. A cumulative concentration-response curve for R-alpha-methylhistamine was made; when a second curve was made 30 min afterwards, a marked decrease of pD2 and a more modest decrease of Emax were observed without changes in tissue sensitivity to electrical stimulation or morphine inhibition. At 120 min, pD2 and Emax were not different from those for the first curve. Receptor desensitization seems homologous and reversible and could interfere with repetitive testing of histamine H3 receptor ligands.     

Histamine, acting via H3 receptors, inhibits somatostatin and stimulates acid secretion in isolated mouse stomach

BACKGROUND & AIMS: The role of histamine H3 receptors in the regulation of gastric acid secretion is unclear. The present study was designed to characterize the location of H3 receptors in the fundus of the stomach and the mechanism by which these receptors regulate acid secretion. METHODS: Acid, somatostatin, and histamine secretions were measured in the isolated mouse stomach. RESULTS: Thioperamide (H3 antagonist) increased somatostatin and decreased histamine and acid secretion in a concentration-dependent manner. (r)-alpha-Methylhistamine (H3 agonist) had the opposite effect, decreasing somatostatin and increasing histamine and acid secretion. The pattern implies that endogenous histamine, acting via H3 receptors, exerts an inhibitory paracrine influence on somatostatin secretion. Somatostatin antibody increased basal histamine secretion and abolished the decrease in histamine and acid secretion induced by thioperamide, confirming that changes in histamine and acid secretion induced by the activation of H3 receptors reflected changes in somatostatin secretion. Similar effects were obtained when acid secretion was stimulated by histamine: thioperamide augmented somatostatin and thus inhibited acid secretion, and (r)-alpha-methylhistamine attenuated somatostatin and increased acid secretion. CONCLUSIONS: Reciprocal inhibitory paracrine pathways link histamine and somatostatin cells in the gastric fundus. Histamine, acting via H3 receptors, augments acid secretion by eliminating the inhibitory influence of somatostatin.     

Differences in affiliative behavior of weanling rats selecting eating and drinking sites.

In 3 experiments with Long-Evans rats, the presence of an adult at a feeding site profoundly influenced a conspecific weanling's probability of eating there. Presence of an adult at a drinking site did not have a comparable effect. This indicates that the influence of adult presence at a feeding site on pup feeding site selection, reported in previous studies, is not simply an epiphenomenon reflecting a general affiliative tendency of rat pups. Rather, social affiliation appears to be a factor of special importance in the feeding site selection of young rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of amygdaloid lesions on eating elicited by cortical spreading depression

The investigations were carried out in 296 patients with myocardial infarction (238 men and 58 women) aged 24-91 years, admitted to an intensive care unit on the 1st or 2nd day of the disease. In all patients the catheter for determination of central venous pressure was introduced into the right atrium through the cephalic vein the the first 100 cases, and through the subclavian vein in 196 cases. The catheter was kept in the atrium for 3-4 days. Values of c.v.p. between 50 and 120 mm Hg were accepted as normal.     

Relation of drinking and eating to masculinity and femininity

The relationship between desirable and undesirable aspects of masculinity and femininity and drinking and eating was investigated. A sample of 144 university women in Australia completed questionnaires that assessed masculinity and femininity, reported drinking, alcohol dependence, eating restraint, frequency of dieting, and overeating. Evidence of a common underlying dimension linking aspects of problem drinking and overeating to undesirable masculine characteristics was found. The results are consistent with the view that women engage in excessive consummatory behaviors such as binging to deal with their gender-role conflict.     

Modulation of [3H]quinpirole binding to dopaminergic receptors by adenosine A2A receptors

Alteration of ligand binding to dopamine D2 receptors through activation of adenosine A2A receptors in rat striatal membranes has been studied by means of kinetic analysis. The binding of dopaminergic agonist [3H]quinpirole to rat striatal membranes was characterized by the constants Kd = 1.50+/-0.09 nM and Bmax = 115+/-2 fmol/mg of protein. The kinetic analyses revealed that the binding had at least two consecutive and kinetically distinguishable steps, the fast equilibrium of complex formation between receptor and agonist (KA = 5.9+/-1.7 nM), followed by a slow isomerization equilibrium (Ki = 0.06). Activation of adenosine A2A receptors by CGS 21680 caused enhancement of the rate [3H]quinpirole binding, altering mainly the formation of the receptor-ligand complexes (KA) as well as the isomerization rate of this complexes (ki), while the deisomerization rate (k[-i]) and the apparent dissociation rate remained unchanged.     

Histamine H3 receptors--general characterization and their function in the cardiovascular system

The histamine H3 receptor was initially identified as a presynaptic autoreceptor controlling histamine release and synthesis in the brain. It belongs to the superfamily of G protein-coupled receptors. The existence of the H3 receptor which has not yet been cloned was definitely established by the design of highly potent and selective agonists (R-(-)-alpha-methylhistamine, imetit) and antagonists (thioperamide, clobenpropit). These receptors also occur as heteroreceptors both in the central nervous system and on peripheral neurons of the gastrointestinal and bronchial tract, where they regulate the release of a variety of neurotransmitters. In the cardiovascular system, histamine H3 receptors are mainly located presynaptically on the postganglionic sympathetic nerve fibers innervating the blood vessels and the heart. Their activation leads to the inhibition of noradrenaline release and consequently to the reduction of the neurogenic vasopressor and cardiostimulatory responses. The presence of such receptors has been shown both in vitro (human, pig, guinea-pig, rabbit, rat isolated tissues) and in vivo (rat, guinea-pig). The vascular and cardiac presynaptic H3 receptors may be activated by endogenous histamine. The vascular H3 receptors appear to be operative in hypertension and interact with presynaptic alpha 2-adrenoceptors. Postsynaptic vasodilatatory H3 receptors have been detected in several vascular beds as well. H3 receptor ligands affect basal cardiovascular parameters in conscious and anesthetized guinea-pigs but not rats. Presynaptic H3 receptors may play a role in the pathophysiology of headache and cardiac ischemia.     

In vivo and in vitro regulation of [3H]glyburide binding to brain sulfonylurea receptors in obesity-prone and resistant rats by glucose

Select brain neurons increase their firing rate when ambient glucose levels rise, possibly via a neuronal ATP-sensitive K+ (KATP) channel and its associated sulfonylurea receptor (SUR). We used receptor autoradiographic binding of 20 nM [3H]glyburide (in the presence or absence of Gpp(NH)p which blocks binding to low-affinity sites) to assess the in vivo and in vitro effects of altering glucose availability upon high- and low-affinity binding to brain SUR. Since the brain's ability to monitor and regulate glucose metabolism is critical to maintenance of energy balance, testing was done in chow-fed male Sprague-Dawley rats which had an underlying predisposition to develop either diet-induced obesity (DIO-prone) or to be diet-resistant (DR-prone) when subsequently fed a high-energy diet. Under control conditions, both in vivo and in vitro studies showed DIO-prone rats to have reduced levels of low-, but not high-affinity [3H]glyburide binding in most forebrain areas. As compared to equiosmolar infusions of mannitol, 60 min unilateral intracarotid glucose infusions at 4 mg/kg/min in awake rats reduced low-affinity [3H]glyburide binding in numerous hypothalamic and amygdalar areas of both DR- and DIO-prone rats with little effect on high-affinity binding. Only in the paraventricular nucleus of DR-prone rats was there a phenotype-specific downregulation of low-affinity binding. Brain sections from other rats were incubated with [3H]glyburide in the presence of 0, 5 or 10 mM glucose. The resultant in vitro effects of glucose were more variable and widespread than intracarotid infusions. Here, glucose often increased low-affinity [3H]glyburide binding, particularly in DR-prone rats at 5 mM. Again, there was little effect on high-affinity binding. Thus, glucose may affect the firing of glucose-responsive neurons by indirectly altering KATP channel function via its effects on low-affinity cell body SUR.     

Tracheal vascular dilatation elicited by vagal nerve stimulation in rats

We investigated the effects of the electrical stimulation of a unilateral cervical vagal nerve on the blood flow in the trachea using laser Doppler flowmetry in urethane anesthetized Wistar King rats. Stimulation for 30 s at 1, 2, 5, 10, 20 or 50 Hz with 10 V intensity caused an increase in tracheal blood flow (TBF) in a frequency-dependent manner; the effects were most dominant with the 10-Hz stimulation among the six frequencies used. The increased responses of TBF with the muscarinic receptor antagonist atropine (1.0 mg/kg, i.v.) were significantly reduced when compared with those without atropine at 5 Hz stimulation (123.3 +/- 11.9% vs. 180.1 +/- 24.5%). This shows the existence of vasodilation due to a cholinergic mechanism. The increased responses of TBF after the ganglion blocking agent hexamethonium (20 mg/kg) i.v. administration were significantly reduced when compared with those without hexamethonium at 1, 2 Hz stimulation (1 Hz: 18.9 +/- 2.7% vs. 35.4 +/- 4.7%, 2 Hz: 40.5 +/- 8.9% vs. 58.8 +/- 6.7%); this shows the existence of vasodilation due to a non-cholinergic parasympathetic efferent mechanism which itself appears to be due to the release of neuropeptides such as VIP and PHI. The increased responses after hexamethonium administration were augmented probably because of the enhanced release of other neuropeptides like SP and CGRP especially at 10 Hz and 20 Hz stimulation. These findings suggest that the mechanism of vasodilation by the activity in the vagal fibers in the trachea of the rat has cholinergic and non-cholinergic efferent components and a non-cholinergic afferent component. In rats, the afferent component may play an important role in controlling tracheal vascular changes.     

Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors

IL-12 and IL-10, respectively, stimulate Th1 and Th2 immune responses. The development of some allergic reactions, infections, and tumors are associated with excessive histamine production and a shift toward Th2 responses. Here we address the possibility that this association is causally linked, at least in part, to modulation of IL-12 and IL-10 production by histamine. We report that histamine dose-dependently inhibited the secretion of human IL-12 (p70) and increased the production of IL-10 in LPS-stimulated whole blood cultures. These effects of histamine were antagonized by cimetidine, an H2 receptor antagonist, but not by selective H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. The effects of histamine on IL-12 and IL-10 secretion were independent of endogenous secretion of IL-10 or exogenous addition of IL-12, while Ro 20-1724, a phosphodiesterase inhibitor, potentiated the effects of histamine on IL-12 and IL-10 production, implicating cAMP in its actions. Similar modulatory effects of histamine on IL-12 and IL-10 production, which were reversed by the H2 antagonist cimetidine, were observed in PBMC and isolated monocytes stimulated by Staphylococcus aureus Cowan strain 1 and LPS, respectively. Thus, histamine, via stimulation of H2 receptors on peripheral monocytes and subsequent elevation of cAMP, suppresses IL-12 and stimulates IL-10 secretion, changes that may result in a shift of Th1/Th2 balance toward Th2-dominance. This may represent a novel mechanism by which excessive secretion of histamine potentiates Th2-mediated allergic reactions and contributes to the development of certain infections and tumors normally eliminated by Th1-dependent immune mechanisms.     

Taste receptors on the anterior tongue and nasoincisor ducts of rats contribute synergistically to behavioral responses to sucrose.

In 4 groups of rats, behavioral responsiveness to sucrose was tested by allowing them to lick solutions in a computer-controlled gustometer (10-sec trials; 0.01–2.0 M). Rats with cautery lesions of the nasoincisor ducts (NID) behaved no differently from controls. After bilateral chorda tympani nerve (CT) section, which removes taste input from the anterior tongue (AT), rats demonstrated a marginal attenuation in their responsiveness to sucrose. Combining the 2 lesions, however, had the greatest effect on the concentration–response curve. By shifting the curve to the right and lowering the asymptotic licking rate, the combined lesion reduced the area under the curve by one third. The effects of the combined treatments were larger than would be predicted from the sum of either one alone. This presumably reflects the central convergence of primary afferent axons from the NID and AT. Neurophysiological data have demonstrated such convergence within the nucleus of the solitary tract. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain histamine H3 receptors in rats with portacaval anastomosis: in vitro and in vivo studies

The long-term effects of portacaval anastomosis (PCA) on histamine H3 receptors in rat brain were studied by in vitro and in vivo methods. The overflow of histamine from the anterior hypothalamus and from cortex after long-term PCA was determined by in vivo microdialysis. The binding properties of [3H]-R-alpha-methylhistamine in membranes from cortex, cerebellum, and rest of brain (ROB) were examined with saturation binding experiments. The regional distribution of [3H]-R-alpha-methylhistamine binding sites in the brain of sham- and PCA-operated rats was assessed also with autoradiography. The tissue levels of histamine were significantly elevated in cortex and ROB of PCA-operated rats. In addition, the spontaneous and K+-evoked overflow of histamine from anterior hypothalamus, and the thioperamide-induced overflow from both anterior hypothalamus and cortex were increased after chronic PCA. In spite of the significantly elevated tissue concentrations and the moderate increase in histamine release, the binding properties of [3HI-R-alpha-methylhistamine to cortical membranes were not significantly changed. However, the autoradiography study did reveal a decrease in [3H]-R-alpha-methylhistamine binding density, particularly in striatum and cortex, where H3 receptors are located mainly at non-histaminergic neurons. In conclusion, we suggest that there is a region-selective increase in the histaminergic activity in chronic PCA, which leads to the down-regulation of somadendritic and pre-synaptic H3 receptors located at non-histaminergic neurons. At the same time, the autoreceptor mediated control of histamine neuronal activity via pre-synaptic H3 receptors located at histaminergic neurons is preserved after long-term PCA.     

Modulation of pentagastrin-induced histamine release by histamine H3 receptors in the dog

BACKGROUND: The histamine H3 receptor has been shown to inhibit pentagastrin-induced gastric acid secretion in dogs. Since pentagastrin releases histamine in dogs, we have now assessed whether the effects of H3-receptor ligands may be indirectly mediated by changes in gastric histamine release. METHODS: Pentagastrin infusions (1 or 6 micrograms/kg/h), alone or together with the H3-receptor agonist (R) alpha-methylhistamine (1.2 mumol/kg/h) or the antagonist thioperamide (0.1 mumol/kg/h), were performed in dogs. One group (anaesthetized) was used for enzyme immunoassays of plasma histamine and, when required. (R) alpha-methylhistamine in the gastrosplenic vein, and another group (non-anaesthetized) for measurement of gastric acid secretion. RESULTS: Histamine levels were increased five- and eight-fold after 1 and 6 micrograms/kg/h pentagastrin, respectively, whereas acid output was nearly maximal at the lower dosage. (R) alpha-methylhistamine, at a plasma concentration of 0.15 microM, inhibited histamine release by 78% (P < 0.007) and 37% (not significant) and the total acid output by 44% (P < 0.05) and 19% (not significant) after infusion of 1 and 6 micrograms/kg/h pentagastrin, respectively. Thioperamide, together with pentagastrin in low dose, significantly increased histamine release by 212% (P < 0.05), whereas acid output increased by 34% (not significant). CONCLUSIONS: The histamine H3 receptor mediates a negative feedback control of pentagastrin-induced release of gastric histamine. It is tonically activated by endogenous histamine after pentagastrin in low dosage. The control of acid secretion by the H3 receptor seems to involve modulation of endogenous histamine release, possibly by means of enterochromaffin-like cells.     

Histamine chloramines have a persistent stimulating effect on histamine H2 receptors and gastric acid secretion

A strong association of hepatitis C infection (HCV) with 'essential' mixed cryoglobulinaemia has been established. The demonstration of HCV in Type II mixed cryoglobulins with monoclonal rheumatoid factors (mRF) that bear the WA crossidiotype has lead to the hypothesis that mixed cryoglobulins result from chronic stimulation by HCV-lipoprotein of a population of XId WA+B-1a cells. The reactivity of WA IgM initially produced is with the HCV-self antigen complex with RF activity resulting secondarily from the pausi-mutational process accompanying the T cell independent process. This benign proliferation progresses by multi step mutations to malignancy in a minority of patients. The implications of the hypothesis for understanding the physiology of certain natural auto antibodies and for therapeutic intervention in this disease are discussed.     

Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats

Experiments were carried out to characterize the cardiorespiratory reflex responses to intravenous injection of lactic acid and to determine the involvement of vagal bronchopulmonary C-fiber afferents in eliciting these responses in anesthetized rats. Bolus injection of lactic acid (0.2 mmol/kg i.v.) immediately elicited apnea, bradycardia, and hypotension, which were then followed by a sustained hyperpnea. The immediate apneic and bradycardiac responses to lactic acid were completely abolished by bilateral vagotomy and were absent when the same dose of lactic acid was injected into the left ventricle. The subsequent hyperpneic response was substantially attenuated by denervation of carotid body chemoreceptors. After a perineural capsaicin treatment of both vagus nerves to block the conduction of C fibers, lactic acid no longer evoked the immediate apnea and bradycardia, whereas the hyperpneic response became more pronounced and sustained, presumably because of the removal of the inhibitory effect on breathing mediated by pulmonary C-fiber activation. Single-unit electrophysiological recording showed that intravenous injection of lactic acid consistently evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs. In conclusion, the cardiorespiratory depressor responses induced by lactic acid are predominantly elicited by activation of vagal pulmonary C fibers.     

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.     

Hypothalamic and midbrain neural pathways involved in eating, drinking, irritability, aggression, and copulation in rats.

Investigated in 3 experiments with male hooded rats (N = 61) the effects of parasagittal cuts placed at 3 anterior-posterior positions. Cuts that separated portions of the medial from the lateral hypothalamus produced severe hyposexuality if they lay lateral to the medial preoptic-anterior hypothalamic continuum. Hyperphagia, irritability, and modest sexual impairment were produced if the cuts lay lateral to the anterior tips of the ventromedial hypothalamic nuclei and slightly invaded the anterior hypothalamus. Posterior, but not anterior, medial-forebrain-bundle (MFB) cuts disrupted copulation. Central gray cuts resulted in slight hyperphagia, and reticular formation cuts resulted in hyposexuality. It is concluded that the medial hypothalamic nuclei exert their effects on eating, irritability, and copulation through their lateral connections with the lateral hypothalamus and those components of the MFB that descend on (or ascend from) the lower brainstem. (40 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)