Central administration of zinc reduces salt intake in rats

The aim of the present study was to investigate the effect of third ventricle injections of zinc on salt intake in rats in the three different experimental models where sodium appetite is increased: fluid deprivation, central angiotensinergic stimulation and sodium depletion. Adult Wistar male rats received third ventricle injections of Zn(Ac)2 in three different doses (0.03, 0.3 and 3.0 nmol/rat). Central angiotensinergic stimulation was achieved by third ventricle injections of angiotensin II in the dose of 25 ng/rat 30 min before central zinc administration. As expected, fluid deprivation, central angiotensinergic stimulation and sodium depletion significantly increased sodium appetite. Water intake was also enhanced after fluid deprivation and central angiotensinergic stimulation. After sodium depletion, no increase in water intake was observed. Third ventricle injections of zinc inhibited salt intake in all three experimental models studied. Water intake was also inhibited by central zinc administration after fluid deprivation and central angiotensinergic stimulation. Conversely, third ventricle injections of zinc were unable to modify food intake or body temperature. It is suggested that zinc, acting on central structures related to the control of body fluid homeostasis, inhibits the drive for salt intake that is normally observed during fluid deprivation, central angiotensinergic stimulation and sodium depletion.     

Central H1 and H2 receptor participation in the control of water and salt intake in rats

The aim of the present study was to evaluate the participation of brain H1 and H2 histaminergic receptors on water and salt intake induced by water deprivation (24 h), furosemide-induced sodium depletion and central angiotensinergic pharmacological stimulation in rats. Third ventricle injections of the H1 and H2 receptor antagonists, mepyramine (50, 100, 200 and 400 nmol) and cimetidine (100, 200 and 400 nmol), were unable to modify water intake induced by water deprivation and sodium depletion. Salt intake elicited by water deprivation and sodium depletion was reduced by the central administration of mepyramine, while intracerebroventricular administration of cimetidine had no effect. Water and salt intake evoked by central angiotensinergic stimulation (10 ng) was diminished by third ventricle injections of both mepyramine and cimetidine. Inhibition of the ingestive behaviors observed here is not a result of any illness-like effect produced by the intracerebroventricular injections of the histaminergic antagonists used, as demonstrated by an avoidance test. It was also shown that third ventricle injections of these compounds were unable to modify the hedonic behavior that leads rats to drink a tasty saccharin solution. We conclude that central histaminergic receptors participate in the control of salt intake induced by distinct physiological and pharmacological stimuli.     

Central kappa opioid receptors modulate salt appetite in rats

The role of the central opioid system in the control of water and salt intake is complex, with both stimulatory and inhibitory effects having been observed. The aim of the present study was to investigate the participation of the central κ-opioid receptors in the control of salt appetite. Male Wistar rats were submitted to two different experimental protocols: sodium deficit produced by the diuretic, furosemide, and brain angiotensinergic stimulation in rats under normal sodium balance. Lateral ventricle (LV) injections of Nor-binaltorphimine (Nor-BNI) at different doses (5, 10 and 20 nmol) inhibited hypertonic saline solution (1.5%) intake in sodium-depleted rats. The salt appetite induced by an LV injection of angiotensin II (Ang II) (10 ng) was also blocked by Nor-BNI injections into the LV, while no significant change was observed in water intake. Furthermore, the decrease in salt intake seems not to have been due to a general inhibition of locomotor activity or to any change in palatability, since central administration of Nor-BNI failed to modify the intake of a 0.1% saccharin solution when the animals were submitted to a "dessert test" or to induce any significant locomotor deficit in the open-field test. Also the central administration of Nor-BNI was unable to modify blood pressure in sodium-depleted animals. The present results suggest that activation of endogenous κ-opioid receptors modulates salt appetite induced by sodium depletion and by central angiotensinergic stimulation in rats.     

Involvement of central H1 and H2 receptors in water intake induced by hyperosmolarity, hypovolemia and central cholinergic stimulation

In the present study we investigated the participation of central H1 and H2 histaminergic receptors in water intake induced by hyperosmolarity (evoked by intragastric salt load), by hypovolemia (promoted by the subcutaneous administration of polyethyleneglycol) and by the pharmacological stimulation of central cholinergic pathways by the muscarinic agonist carbachol in male Wistar rats. The data presented here show that the pharmacological blockade of central H1 histaminergic receptors by third ventricle injections of mepyramine significantly decreased water intake induced by hyperosmolarity, hypovolemia and by the intracerebroventricular injections of carbachol. On the other hand, the pharmacological blockade of central H2 histaminergic receptors by third ventricle injections of cimetidine significantly reduced water intake in hypovolemic and hyperosmotic animals, but failed to alter water intake induced by central cholinergic stimulation by carbachol. We conclude that H1 and H2 brain histaminergic receptors are involved in inducing thirst during hyperosmolarity and hypovolemia and that H1 histaminergic receptors located post-synaptically in relation to cholinergic pathways seem to be important in triggering drinking following central pharmacological cholinergic stimulation.     

Atrial natriuretic polypeptides: structure-activity relationship in the central action--a comparison of their antidipsogenic actions

The structure-activity relationship of atrial natriuretic polypeptides (ANPs) in the central action was investigated by examining the suppressive effects of the intracerebroventricular (i.c.v.) administration of ANPs on water intake induced by the i.c.v. injection of angiotensin II (AII) (0.1 nmol) in rats. alpha-Rat ANP (alpha-rANP), alpha-human ANP, alpha-rANP4-28 and alpha-rANP5-28 at a dose of 1.5 nmol exerted equipotent antidipsogenic actions, while alpha-rANP7-23-amide had no inhibitory effect on water drinking at this dose.     

Vanadate stimulates in vivo glucose uptake in brain and arrests food intake and body weight gain in rats

Vanadate, administered via drinking fluid (0.2-0.8 mg/ml in 80 mM NaCl), attenuated food intake and strongly suppressed body weight gain in normally-fed or 20-hour food-deprived rats. At 0.8 mg/ml for 4 days, oral vanadate significantly stimulated the rate of hexose uptake by brain tissue. When microinjected into the lateral cerebral ventricle at a dose of 82 nmol, vanadate strongly and specifically suppressed food intake and body weight gain in 20-hour food deprived rats previously maintained on tap water. This inhibitory effect was reversed by coadministration of 3-O-methyl glucose. Collectively, the results suggest that vanadate is capable of blocking food intake by a specific effect in the central nervous system that involves stimulation of local glucose uptake.     

Effect of chronic activation of 5-HT3 receptors on 5-HT3, 5-HT1A and 5-HT2A receptors functional activity and expression of key genes of the brain serotonin system

Among serotonin (5-HT) receptors, the 5-HT₃ receptor is the only ligand-gated ion-channel. Little is known about the interaction between the 5-HT₃ receptor and other 5-HT receptors and influence of 5-HT₃ chronic activation on other 5-HT receptors and the expression of key genes of 5-HT system. Chronic activation of 5-HT₃ receptor with intracerebroventricularly administrated selective agonist 1-(3-chlorophenyl)biguanide hydrochloride (m-CPBG) (14 days, 40 nmol, i.c.v.) produced significant desensitization of 5-HT₃ and 5-HT_1A receptors. The hypothermic responses produced by acute administration of selective agonist of 5-HT₃ receptor (m-CPBG, 40 nmol, i.c.v.) or selective agonist of 5-HT_1A receptor (8-hydroxy-2-(di-n-propylamino)tetralin) (8-OH-DPAT, 1 mg/kg, i.p.) was significantly lower in m-CPBG treated mice compared with the mice of control groups. Chronic m-CPBG administration failed to induce any significant change in the 5-HT_2A receptor functional activity and in the expression of the gene encoding 5-HT_2A receptor. Chronic activation of 5-HT₃ receptor produced no considerable effect on the expression on 5-HT₃, 5-HT_1A, and 5-HT transporter (5-HTT) and tryptophan hydroxylase-2 (TPH-2) genes – the key genes of brain 5-HT system, in the midbrain, frontal cortex and hippocampus. In conclusion, chronic activation of ionotropic 5-HT₃ receptor produced significant desensitization of 5-HT₃ and postsynaptic 5-HT_1A receptors but caused no considerable changes in the expression of key genes of the brain 5-HT system.     

Use of peripheral blood transcriptome biomarkers for epilepsy prediction

Fenfluramine reduces hunger and promotes body weight loss by increasing central serotonin (5-HT) signaling. More recently, neuropeptides have been linked to the regulation of feeding behavior, metabolism and body weight. To examine possible interactions between 5-HT and neuropeptides in appetite control, fenfluramine (200 nmol/0.5 μl/side) was administered directly into the hypothalamic paraventricular nuclei (PVN) of male rats. Bilateral fenfluramine produced significant hypophagia and increased expression of PVN corticotropin releasing factor (CRF) mRNA and neuropeptide Y (NPY) mRNA in the arcuate nucleus within the first hour after drug administration. Fenfluramine's effects on feeding behavior and mRNA expression were blocked by PVN injections of a 5-HT(1-2) receptor antagonist, metergoline (15 nmol/0.5 μl/side). These data suggest that 5-HT neurons targeting hypothalamic paraventricular CRF neurons may participate in an appetite control circuit for reducing food intake.     

Some central mechanisms of thirst in the dog.

Measurements of water intake were made on a population of trained conscious dogs of both sexes prepared with chronic third ventricle cannulae. 2. Injection of 100 ng angiotensin II into the third ventricle lead to a prompt stimulation of drinking, the mean water intake over a 5 min period being 503 +/- 89 ml. (n=6) compared with controls. This dipsogenic effect of angiotensin II was abolished by prior central administration of 10 mug saralasin acetate or 100 ng atropine. 3. Injection of 1 mug carbachol into the third ventricle produced a small, variable increase in drinking. 4. Injection of 0-2 ml. 5% NaCl into the third ventricle stimulated drinking, a response that was not affected by prior administration of 10 mug saralasin acetate or 100 ng atropine. 5. Following a 24 hr period of water deprivation there was an increase in plasma osmolality and plasma-renin activity. The drinking following this period of water deprivation was not affected by prior control administration of either 10 mug saralasin acetate or 100 ng atropine. 6. In two acute dogs, intracarotid infusion of 125I angiotensin II was not followed by significant appearance of radioactivity in the third ventricle or cisterna magna c.s.f. 7. The relevance of these results to the control of water intake is discussed.     

The effects of metergoline and 8-OH-DPAT injections into arcuate nucleus and lateral hypothalamic area on feeding in female rats during the estrous cycle

The present study examined the effects of local injections of metergoline (MET, an antagonist of 5-HT1/2 receptors, 2 and 20 nmol) and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, selective 5-HT1A receptor agonist, 0.6 and 6 nmol) into the arcuate nucleus (ARC) and the lateral hypothalamus (LH), on ingestive and non-ingestive behaviors of female rats. These effects were examined during the diurnal periods of diestrus and estrus in rats adapted to eat a wet mash diet (enriched with 10% sucrose) during 1h for 3 consecutive days at the recording chamber. The results showed that 8-OH-DPAT injected into the LH significantly reduced food intake at all doses and both cycle stages, while in the ARC these treatments evoked hypophagia only at the highest 8-OH-DPAT dose and only at the estrous phase. MET administered into the ARC (at all doses) failed to affect food intake during both estrous stages. On the other hand, food intake decreased after injection of both doses of MET into the LH of rats during estrous and diestrus phases. In estrus stage, injections of the higher dose of 8-OH-DPAT into the ARC and into the LH decreased the duration of feeding. Latency to start feeding, drinking, and non-ingestive behaviors were not affected by 8-OH-DPAT or MET treatments in the ARC or the LH in both cycle phases. These results indicated that 5-HT1A receptors participate in the serotonergic control of feeding-related mechanisms located at the ARC and the LH. These feeding-related serotonergic circuits in both areas are possibly affected by ovarian hormones that could increase sensitivity of ARC neurons to the hypophagic effects of 8-OH-DPAT or increase the efficacy of satiety signals that terminate feeding. In addition, the present data indicated that serotonergic inputs do not exert a tonic inhibitory activity on the ARC and the LH feeding-related circuits.     

Temperature effects produced in dogs and monkeys by injections of monoamines and related substances into the third ventricle

1. In dogs the effects on rectal temperature of noradrenaline, adrenaline, 5-hydroxytryptamine (5-HT) and of the monoamine oxidase inhibitor tranylcypromine were studied following their injection into the third ventricle through a chronically implanted cannula. Tranylcypromine was given also by the intraperitoneal route.2. The hypothermic effect of the catecholamines and the hyperthermic effect of 5-HT previously demonstrated in anaesthetized dogs were obtained also in an unanaesthetized dog, but 5-HT was effective only in doses under 20 mug.3. Tranylcypromine (1 mg) injected into the third ventricle of dogs anaesthetized with pentobarbitone sodium produced shivering and a rise in temperature.4. Tranylcypromine (10 mg/kg) injected intraperitoneally caused a rise in temperature in the unanaesthetized dog. For a time shivering and panting, two effects which produce opposite change in temperature, were observed together. When injected shortly before an intraperitoneal injection of an anaesthetizing dose of pentobarbitone sodium, tranylcypromine not only prevented the fall in temperature which is normally produced by the anaesthetic but caused a greater and longer lasting rise than when given alone.5. The intraperitoneal injections of tranylcypromine produced profuse salivation, a peripheral effect which persisted after acute denervation and which was not abolished by atropine or tolazoline.6. In rhesus monkeys anaesthetized with intraperitoneal pentobarbitone sodium, noradrenaline, adrenaline, 5-HT and 5-hydroxytryptophan (5-HTP) were injected into the cannulated third ventricle. The catecholamines caused a fall in rectal temperature. No evidence was obtained that the fall resulted from a rise in hypothalamic temperature. The injections of 5-HT or of its precursor 5-HTP raised rectal temperature. Monkeys thus respond to the monoamines injected intraventricularly, in the same way as cats and dogs, and unlike rabbits, sheep, goats, oxen and rats.     

5-HT2 and 5-HT3 receptors in the lateral parabrachial nucleus mediate opposite effects on sodium intake

The present study investigated the role of several 5-HT receptor subtypes in the lateral parabrachial nucleus (LPBN) in the control of sodium appetite (i.e. NaCl consumption). Male Holtzman rats had cannulas implanted bilaterally into the LPBN for the injection of 5-HT receptor agonists and antagonists in conjunction with either acute fluid depletion or 24-h sodium depletion. Following these treatments, access to 0.3 M NaCl was provided and the intakes of saline and water were measured for the next 2 h. Bilateral injections of the 5-HT2A receptor antagonist, ketanserin or the 5-HT2C receptor antagonist, mianserin into the LPBN increased 0.3 M NaCl intake without affecting water intake induced by acute fluid-depletion. Bilateral injections of the 5-HT2B receptor agonist, BW723C86 hydrochloride, had no effect on 0.3 M NaCl or water intake under these conditions. Treatment of the LPBN with the 5-HT2B/2C receptor agonist, 2-(2-methyl-4-clorophenoxy) propanoic acid (mCPP) caused dose-related reductions in 0.3 M NaCl intake after 24 h sodium depletion. The effects of mCPP were prevented by pretreating the LPBN with the 5-HT2B/2C receptor antagonist, SDZSER082. Activation of 5-HT3 receptors by the receptor agonist, 1-phenylbiguanide (PBG) caused dose-related increases in 0.3 M NaCl intake. Pretreatment of the LPBN with the 5-HT3 receptor antagonist, 1-methyl-N-[8-methyl-8-azabicyclo (3.2.1)-oct-3-yl]-1H-indazole-3-carboxamide (LY-278,584) abolished the effects of PBG, but LY-278,584 had no effects on sodium or water intake when injected by itself. PBG injected into the LPBN did not alter intake of palatable 0.06 M sucrose in fluid replete rats. The results suggest that activation of the 5-HT2A and 5-HT2C receptor subtypes inhibits sodium ingestion. In contrast, activation of the 5-HT3 receptor subtype increases sodium ingestion. Therefore, multiple serotonergic receptor subtypes in the LPBN are implicated in the control of sodium intake, sometimes by mediating opposite effects of 5-HT. The results provide new information concerning the control of sodium intake by LPBN mechanisms.     

GABA(A) receptor activation in the lateral parabrachial nucleus induces water and hypertonic NaCl intake

Inhibitory serotonergic and cholecystokinergic mechanisms in the lateral parabrachial nucleus and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. In the present study we investigated if the GABA(A) receptors in the lateral parabrachial nucleus are involved in the control of water, NaCl and food intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. Bilateral injections of muscimol (0.2 nmol/0.2 microl) into the lateral parabrachial nucleus strongly increased 0.3 M NaCl (20.3+/-7.2 vs. saline: 2.6+/-0.9 ml/180 min) without changing water intake induced by the treatment with the diuretic furosemide combined with low dose of the angiotensin converting enzyme inhibitor captopril s.c. In euhydrated and satiated rats, bilateral lateral parabrachial nucleus injections of muscimol (0.2 and 0.5 nmol/0.2 microl) induced 0.3 M NaCl intake (12.1+/-6.5 and 32.5+/-7.3 ml/180 min, respectively, vs. saline: 0.4+/-0.2 ml/180 min) and water intake (5.2+/-2.0 and 7.6+/-2.8 ml/180 min, respectively, vs. saline: 0.8+/-0.4 ml/180 min), but no food intake (2+/-0.4 g/240 min vs. saline: 1+/-0.3 g/240 min). Bilateral lateral parabrachial nucleus injections of the GABA(A) antagonist bicuculline (1.6 nmol/0.2 microl) abolished the effects of muscimol (0.5 nmol/0.2 microl) on 0.3 M NaCl and water intake. Muscimol (0.5 nmol/0.2 microl) into the lateral parabrachial nucleus also induced a slight ingestion of water (4.2+/-1.6 ml/240 min vs. saline: 1.1+/-0.3 ml/240 min) when only water was available, a long lasting (for at least 2 h) increase on mean arterial pressure (14+/-4 mm Hg, vs. saline: -1+/-1 mm Hg) and only a tendency to increase urinary volume and Na+ and K+ renal excretion. Therefore the activation of GABA(A) receptors in the lateral parabrachial nucleus induces strong NaCl intake, a small ingestion of water and pressor responses, without changes on food intake.     

Antidipsogenic action of alpha-human atrial natriuretic polypeptide administered intracerebroventricularly in rats

Intracerebroventricular (i.c.v.) administration of alpha-human atrial natriuretic polypeptide (alpha-hANP) in a dose of 5 micrograms did not change water intake in normal rats, while 0.1 micrograms of angiotensin II (AII) and 0.5 micrograms of carbachol caused a marked increase in water intake for 30 min after i.c.v. injections. The water intake induced by 0.1 micrograms of AII was significantly suppressed by the simultaneous administration of 2 and 5 micrograms of alpha-hANP. However, alpha-hANP did not affect the water intake caused by 0.5 micrograms of carbachol. In 24-h water-deprived rats, alpha-hANP in doses of 2 and 5 micrograms pronouncedly inhibited the water intake. alpha-hANP did not change the food intake in 24-h fasted rats nor the locomotor activity in normal rats. These findings suggest that alpha-hANP in the central nervous system may play an important role in controlling drinking behavior, interacting with AII.     

Apolipoprotein E reduces food intake via PI3K/Akt signaling pathway in the hypothalamus

Apolipoprotein E (apoE) is a satiation factor. While central apoE administration reduces food intake, the specific intracellular signaling mechanisms activated by apoE remain largely unknown. Using primary cultured hypothalamic neurons, we demonstrated that apoE treatment (50 nM) elicited rapid activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling cascade. Specifically, apoE induced the phosphorylation of Akt, peaking at 30 min, and the increased phosphorylation of Akt was significantly attenuated after pretreatment with LY294002 (50 μM), an inhibitor of the PI3K signaling pathway. To determine whether the activation of PI3K by apoE is required for the ability of apoE to reduce food intake, LY294002 (1 nmol) was infused into the 3rd-cerebral ventricle before injection of an anorectic dose of apoE. Consistent with our previous report, apoE (4 μg) exerted significant reduction of food intake in the 4-h fasted rats, compared with saline. Pretreatment with LY294002 significantly attenuated the potency of exogenous apoE to induce satiation, while the same dose of PI3K inhibitor by itself caused only a slight non-significant decrease of food intake. These results indicate that the activation of the PI3K/Akt pathway is necessary for the acute effects of apoE on food intake.     

Opioid activation in the lateral parabrachial nucleus induces hypertonic sodium intake

Opioid mechanisms are involved in the control of water and NaCl intake and opioid receptors are present in the lateral parabrachial nucleus (LPBN), a site of important inhibitory mechanisms related to the control of sodium appetite. Therefore, in the present study we investigated the effects of opioid receptor activation in the LPBN on 0.3 M NaCl and water intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normohydrated and satiated rats, bilateral injections of the opioid receptor agonist beta-endorphin (2 nmol/0.2 mul) into the LPBN induced 0.3 M NaCl (17.8+/-5.9 vs. saline: 0.9+/-0.5 ml/240 min) and water intake (11.4+/-3.0 vs. saline: 1.0+/-0.4 ml/240 min) in a two-bottle test. Bilateral injections of the opioid antagonist naloxone (100 nmol/0.2 mul) into the LPBN abolished sodium and water intake induced by beta-endorphin into the LPBN and also reduced 0.3 M NaCl intake (12.8+/-1.5 vs. vehicle: 22.4+/-3.1 ml/180 min) induced by 24 h of sodium depletion (produced by the treatment with the diuretic furosemide s.c.+sodium deficient food for 24 h). Bilateral injections of beta-endorphin into the LPBN in satiated rats produced no effect on water or 2% sucrose intake when water alone or simultaneously with 2% sucrose was offered to the animals. The results show that opioid receptor activation in the LPBN induces hypertonic sodium intake in satiated and normohydrated rats, an effect not due to general ingestive behavior facilitation. In addition, sodium depletion induced 0.3 M NaCl intake also partially depends on opioid receptor activation in the LPBN. The results suggest that deactivation of inhibitory mechanisms by opioid receptor activation in the LPBN releases sodium intake if excitatory signals were activated (sodium depletion) or not.     

Neuropeptide K (NPK) suppresses copulatory behavior in male rats

Recent studies show that neuropeptide K (NPK), a member of the tachykinin family of neuropeptides, is found in various hypothalamic sites implicated in the control of gonadotropin secretion, food intake and sexual behavior. Since our previous studies showed that NPK inhibited feeding and gonadotropin secretion in rats, we have now assessed the effects of NPK on sexual behavior in male rats. Copulatory behavior was recorded subsequent to injection of different doses of NPK either into the third ventricle of the brain or intraperitoneally in sexually experienced male rats. We observed that intraventricular (IVT) administration of 0.125 nmol NPK produced only a slight effect on behavior as indicated by a significant increase in intromission latency. However, a four-fold higher dose of 0.5 nmol of NPK completely eliminated copulatory behavior. These rats displayed no overt locomotor deficit but ignored the receptive females, rarely approaching them during the test period. Only two mounts and no intromissions were observed in 6 rats during the test period. In contrast, neither the same dose of 0.5 nmol nor a higher dose of 3.14 nmol injected intraperitoneally produced any discernible effect on sexual performance. These results show that NPK acts centrally to inhibit sexual behavior in male rats and that hypothalamic NPK may be an important part of the neural circuit that regulates reproduction and related behaviors.     

Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats

Estradiol's inhibitory effect on food intake is mediated, in part, by its ability to increase the activity of meal-related signals, including serotonin (5-HT), which hastens satiation. The important role that postsynaptic 5-HT(2C) receptors play in mediating 5-HT's anorexigenic effect prompted us to investigate whether a regimen of acute estradiol treatment increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized (OVX) rats. We demonstrated that intraperitoneal and intracerebroventricular (i.c.v.) administration of low doses of the 5-HT(2C) receptor agonist meta-chlorophenylpiperazine (mCPP) decreased 1-h dark-phase food intake in estradiol-treated, but not oil-treated, OVX rats. During a longer feeding test, we demonstrated that i.c.v. administration of mCPP decreased 22-h food intake in oil-treated and, to a greater extent, estradiol-treated OVX rats. In a second study, we demonstrated that estradiol increased 5-HT(2C) receptor protein content in the caudal brainstem, but not hypothalamus, of OVX rats. We conclude that a physiologically-relevant regimen of acute estradiol treatment increases sensitivity to mCPP's anorexigenic effect. Our demonstration that this same regimen of estradiol treatment increases 5-HT(2C) receptor protein content in the caudal hindbrain of OVX rats provides a possible mechanism to explain our behavioral findings.     

Effects of lesions of the ventral ventral median preoptic nucleus or subfornical organ on drinking and salt appetite after deoxycorticosterone acetate or yohimbine.

Lesions of the ventral ventral median preoptic nucleus (VVMnPO) enhanced daily salt appetite induced by subcutaneous (sc) injections of deoxycorticosterone acetate (DOCA) but did not affect acute salt appetite or water intake after sc injections of 5 mg/kg of the alpha-2-adrenoreceptor blocker yohimbine. Lesions of the subfornical organ (SFO) or its rostral fiber pathways had no effect on fluid intakes during DOCA treatments but significantly reduced water intake after yohimbine. These findings extend those of a previous report (Fitts, Tjepkes, & Bright, 1990) of enhanced DOCA-induced saline intake in VVMnPO-lesioned rats and demonstrate that the effect is specific to lesions of the VVMnPO. The mechanism of the thirst and salt intake elicited by yohimbine is still unclear, but the SFO and its fiber pathways appear to be important for the expression of the water drinking component. Neither lesion reliably affected yohimbine-induced salt appetite.     

Effects of central and peripheral injections of apelin on fluid intake and cardiovascular parameters in rats

Previous studies have indicated that apelin, a novel peptide suggested to have some actions related to angiotensin peptides, has either a dipsogenic or an antidipsogenic effect and either increases or decreases blood pressure. The present study attempts to provide replication or understanding of these disparate effects. Neither central (lateral or third cerebral ventricle) nor peripheral (intravenous) administration of apelin induced water intake in sated rats, nor did it decrease water intake in deprived rats. It also had no effect on sodium appetite. Peripherally injected apelin had a hypotensive action in anesthetized rats, but had no consistent effect in awake, unrestrained rats. We conclude that apelin does not have reliable or robust effects on fluid intake or blood pressure in Sprague-Dawley rats under normal conditions, but discuss the possibility for a role of apelin in fluid homeostasis in selected physiological states.