Sympathetic and angiotensinergic activity in spontaneously hypertensive rats treated with 3-amino-1,2,4-triazole.

Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or spontaneously hypertensive rats (SHRs) is attenuated by increased central H2O2 concentration, produced either by direct H2O2 icv injection or by increased endogenous H2O2 centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280-330 g were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving SHRs. Acute intravenous injection of ATZ (300 mg/kg of body weight) did not modify MAP and HR during the next 4 h, however, the treatment with ATZ (300 mg/kg of body weight twice per day) for 3 days reduced MAP (144 ± 6, vs. saline, 183 ± 13 mmHg), without changing HR. Intravenous hexamethonium (ganglionic blocker) produced a smaller decrease in MAP 4 h after ATZ (-25 ± 3, vs saline -38 ± 4 mmHg). Losartan (angiotensinergic AT1 receptor blocker) produced a significant depressor response 4 h after ATZ (-22 ± 4, vs. saline: -2 ± 4 mmHg) and in 3-day ATZ treated SHRs (-25 ± 5, vs. saline: -9 ± 4 mmHg). The results suggest that the treatment with ATZ reduces sympathetic activity in SHRs and simultaneously increases angiotensinergic activity.

Inhibition of salty taste and sodium appetite by estrogens in spontaneously hypertensive rats.

Estrogen has a well-known effect of reducing salt intake in rats. This mini review focuses on recent findings regarding the interaction of estradiol with brain angiotensin II to control increased sodium palatability that occurs as a result of sodium appetite in spontaneously hypertensive rats.

Chronic administration of catalase inhibitor attenuates hypertension in renovascular hypertensive rats.

AIMS: Reactive oxygen species like hydrogen peroxide (H2O2) are produced endogenously and may participate in intra- and extracellular signaling, including modulation of angiotensin II responses. In the present study, we investigated the effects of chronic subcutaneous (sc) administration of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) on arterial pressure, autonomic modulation of arterial pressure, hypothalamic expression of AT1 receptors and neuroinflammatory markers and fluid balance in 2-kidney, 1clip (2K1C) renovascular hypertensive rats. MATERIALS AND METHODS: Male Holtzman rats with a clip occluding partially the left renal artery and chronic sc injections of ATZ were used. KEY FINDINGS: Subcutaneous injections of ATZ (600 mg/kg of body weight/day) for 9 days in 2K1C rats reduced arterial pressure (137 ± 8, vs. saline: 182 ± 8 mmHg). ATZ also reduced the sympathetic modulation and enhanced the parasympathetic modulation of pulse interval, reducing the sympatho-vagal balance. Additionally, ATZ reduced mRNA expression for interleukins 6 and IL-1ß, tumor necrosis factor-α, AT1 receptor (0.77 ± 0.06, vs. saline: 1.47 ± 0.26 fold change), NOX 2 (0.85 ± 0.13, vs. saline: 1.75 ± 0.15 fold change) and the marker of microglial activation, CD 11 (0.47 ± 0.07, vs. saline, 1.34 ± 0.15 fold change) in the hypothalamus of 2K1C rats. Daily water and food intake and renal excretion were only slightly modified by ATZ. SIGNIFICANCE: The results suggest that the increase of endogenous H2O2 availability with chronic treatment with ATZ had an anti-hypertensive effect in 2K1C hypertensive rats. This effect depends on decreased activity of sympathetic pressor mechanisms and mRNA expression of AT1 receptors and neuroinflammatory markers possibly due to reduced angiotensin II action.

Central muscarinic and LPBN mechanisms on sodium intake.

Central cholinergic activation stimulates water intake, but also NaCl intake when the inhibitory mechanisms are blocked with injections of moxonidine (α2 adrenergic/imidazoline agonist) into the lateral parabrachial nucleus (LPBN). In the present study, we investigated the involvement of central M1 and M2 muscarinic receptors on NaCl intake induced by pilocarpine (non-selective muscarinic agonist) intraperitoneally combined with moxonidine into the LPBN or by muscimol (GABAA agonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN and in the lateral ventricle were used. Pirenzepine (M1 muscarinic antagonist, 1 nmol/1 µl) or methoctramine (M2 muscarinic antagonist, 50 nmol/1 µL) injected intracerebroventricularly (i.c.v.) reduced 0.3 M NaCl and water intake in rats treated with pilocarpine (0.1 mg/100 g of body weight) injected intraperitoneally combined with moxonidine (0.5 nmol/0.2 µL) into the LPBN. In rats treated with muscimol (0.5 nmol/0.2 µL) into the LPBN, methoctramine i.c.v. also reduced 0.3 M NaCl and water intake, however, pirenzepine produced no effect. The results suggest that M1 and M2 muscarinic receptors activate central pathways involved in the control of water and sodium intake that are under the influence of the LPBN inhibitory mechanisms.

Opioid and α2 adrenergic mechanisms are activated by GABA agonists in the lateral parabrachial nucleus to induce sodium intake.

The activation of GABA, opioid or α2 adrenergic mechanisms in the lateral parabrachial nucleus (LPBN) facilitates hypertonic NaCl intake in rats. In the present study, we combined opioid or α2 adrenergic antagonists with GABA agonists into the LPBN in order to investigate if NaCl intake caused by GABAergic activation in normohydrated rats depends on opioid or α2-adrenergic mechanisms in this area. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. Bilateral injections of muscimol or baclofen (GABAA and GABAB agonists, respectively, 0.5 nmol/0.2 µl) into the LPBN induced strong ingestion of 0.3 M NaCl (45.8 ±â€¯7.3 and 21.8 ±â€¯4.8 ml/240 min, respectively) and water intake (22.7 ±â€¯3.4 and 6.6 ±â€¯2.5 ml/240 min, respectively). Naloxone (opioid antagonist, 150 nmol/0.2 µl) into the LPBN abolished 0.3 M NaCl and water intake to muscimol (2.0 ±â€¯0.6 and 0.9 ±â€¯0.2 ml/240 min, respectively) or baclofen (2.3 ±â€¯1.1 and 0.8 ±â€¯0.4 ml/240 min, respectively). RX 821002 (α2 adrenoceptor antagonist, 10 nmol/0.2 µl) into the LPBN reduced 0.3 M NaCl intake induced by the injections of muscimol or baclofen (26.6 ±â€¯8.0 and 10.1 ±â€¯4.9 ml/240 min, respectively). RX 821002 reduced water intake induced by muscimol (7.7 ±â€¯2.9 ml/240 min), not by baclofen. The results suggest that sodium intake caused by gabaergic activation in the LPBN in normohydrated rats is totally dependent on the activation of opioid mechanisms and partially dependent on the activation of α2 adrenergic mechanisms in the LPBN.

Lateral parabrachial nucleus and opioid mechanisms of the central nucleus of the amygdala in the control of sodium intake.

Facilitatory and inhibitory mechanisms in the central nucleus of the amygdala (CeA) and the lateral parabrachial nucleus (LPBN), respectively, are important for the control of sodium and water intake. Here we investigated the importance of the opioid mechanisms in the CeA for water and 0.3M NaCl intake in euhydrated or hyperosmotic rats treated with injections of muscimol (GABAA agonist) or moxonidine (α2 adrenergic/imidazoline agonist) into the LPBN, respectively. Male Holtzman rats (n=4-8/group) with stainless steel cannulas implanted bilaterally in the CeA and in the LPBN were used. The ingestion of 0.3M NaCl and water by euhydrated rats treated with muscimol (0.5nmol/0.2µl) into the LPBN (29.4±2.7 and 15.0±2.4ml/4h, respectively) was abolished by the previous injections of naloxone (opioid antagonist, 40µg/0.2µl) into the CeA (0.7±0.3 and 0.3±0.1ml/4h, respectively). The ingestion of 0.3M NaCl by rats treated with intragastric 2M NaCl (2ml/rat) combined with moxonidine (0.5nmol/0.2µl) into the LPBN (17.0±3.8ml/2h) was also strongly reduced by the previous injections of naloxone into the CeA (3.2±2.5ml/2h). Sucrose intake was not affected by naloxone injections into the CeA, which minimized the possibility of non-specific inhibition of ingestive behaviors with this treatment. The present results suggest that opioid mechanisms in the CeA are essential for hypertonic NaCl intake when the LPBN inhibitory mechanisms are deactivated or attenuated with injections of muscimol or moxonidine in this area.

Short-term cross-sensitizion of need-free sugar intake by combining sodium depletion and hypertonic NaCl intake.

History of sodium depletion cross-sensitizes the effects of drugs of abuse. The objective of the present study was to find out if history of sodium depletion also cross-sensitizes a natural reward such as sugar intake in the rat. Sodium depletion was induced by furosemide combined with removal of ambient sodium for 24 h; it was repeated seven days later. The depletion was immediately followed by 0.3 M NaCl intake in a sodium appetite test (active sodium repletion). Seven days after the last depletion, hydrated and fed (need-free) sucrose-naïve animals were offered 10% sucrose in a first 2-h sucrose test. The sucrose test was repeated once a day in a series of five consecutive days. History of sodium depletion enhanced sucrose intake in the first and second tests; it had no effect from the third to fifth sucrose test. The effect on the initial sucrose intake tests disappeared if the rats did not ingest 0.3 M NaCl in the sodium appetite test. Prior experience with sucrose intake in need-free conditions had no effect on sodium appetite. History of intracellular dehydration transiently influenced sucrose intake in the first sucrose test. We found no evidence for thirst sensitization. We conclude that history of dehydration, particularly that resulting from sodium depletion, combined to active sodium repletion, produced short-term cross-sensitization of sucrose intake in sucrose-naïve rats. The results suggest that the cross-sensitization of sucrose intake related with acquisition of sugar as a novel nutrient rather than production of lasting effects on sugar rewarding properties.

Participation of α2 -adrenoceptors in sodium appetite inhibition during sickness behaviour following administration of lipopolysaccharide.

Sickness behaviour, a syndrome characterized by a general reduction in animal activity, is part of the active-phase response to fight infection. Lipopolysaccharide (LPS), an effective endotoxin to model sickness behaviour, reduces thirst and sodium excretion, and increases neurohypophysial secretion. Here we review the effects of LPS on thirst and sodium appetite. Altered renal function and hydromineral fluid intake in response to LPS occur in the context of behavioural reorganization, which manifests itself as part of the syndrome. Recent data show that, in addition to its classical effect on thirst, non-septic doses of LPS injected intraperitoneally produce a preferential inhibition of intracellular thirst versus extracellular thirst. Moreover, LPS also reduced hypertonic NaCl intake in sodium-depleted rats that entered a sodium appetite test. Antagonism of α2 -adrenoceptors abolished the effect of LPS on sodium appetite. LPS and cytokine transduction potentially recruit brain noradrenaline and α2 -adrenoceptors to control sodium appetite and sickness behaviour.

Importance of the central nucleus of the amygdala on sodium intake caused by deactivation of lateral parabrachial nucleus.

The lateral parabrachial nucleus (LPBN) and the central nucleus of the amygdala (CeA) are important central areas for the control of sodium appetite. In the present study, we investigated the importance of the facilitatory mechanisms of the CeA on NaCl and water intake produced by the deactivation of LPBN inhibitory mechanisms. Male Holtzman rats (n=7-14) with stainless steel cannulas implanted bilaterally in the CeA and LPBN were used. Bilateral injections of moxonidine (α2-adrenoceptor/imidazoline agonist, 0.5 nmol/0.2 µl) into the LPBN increased furosemide+captopril-induced 0.3M NaCl (29.7 ± 7.2, vs. vehicle: 4.4 ± 1.6 ml/2h) and water intake (26.4 ± 6.7, vs. vehicle: 8.2 ± 1.6 ml/2h). The GABAA agonist muscimol (0.25 nmol/0.2 µl) injected bilaterally into the CeA abolished the effects of moxonidine into the LPBN on 0.3M NaCl (2.8 ± 1.6 ml/2h) and water intake (3.3 ± 2.3 ml/2h). Euhydrated rats treated with muscimol (0.5 nmol/0.2 µl) into the LPBN also ingested 0.3M NaCl (19.1 ± 6.4 ml/4h) and water (8.8 ± 3.2 ml/4h). Muscimol (0.5 nmol/0.2 µl) into the CeA also abolished 0.3M NaCl (0.1 ± 0.04 ml/4h) and water intake (0.1 ± 0.02 ml/4h) in euhydrated treated with muscimol into the LPBN. The present results show that neuronal deactivation of the CeA abolishes NaCl intake produced by the blockade of LPBN inhibitory mechanisms, suggesting an interaction between facilitatory mechanisms of the CeA and inhibitory mechanisms of the LPBN in the control of NaCl intake.

Dipyrone attenuates acute sickness response to lipopolysaccharide in mice.

Sickness behavior appears to be the expression of a central motivational state that reorganizes the organism's priorities to cope with infectious pathogens. To evaluate the effect of dipyrone in lipopolysaccharide (LPS)-induced sickness behavior, mice were subjected to the forced swim test (FST), tail suspension test (TST), dark-light box test, open field test, sucrose preference intake test and food intake test. LPS administration increased the immobility time in the TST, increased the time spent floating in the FST, and depressed locomotor activity in the open field test. Treatment with LPS decreased the total number of transitions made between the dark and light compartments of the apparatus and induced anhedonia and anorexia. Pre-treatment with dipyrone (10, 50, or 200 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, open field and light-dark box tests. In addition, dipyrone prevented anhedonia and anorexia in mice challenged with LPS. Considering that dipyrone attenuates LPS-induced behavioral changes, it is proposed that LPS-induced sickness behavior is dependent on the COX pathway.

Changes in taste reactivity to intra-oral hypertonic NaCl after lateral parabrachial injections of an α2-adrenergic receptor agonist.

Bilateral injections of moxonidine, an α2-adrenoceptor and imidazoline receptor agonist, into the lateral parabrachial nuclei (LPBN) enhance sodium appetite induced by extracellular dehydration. In the present study, we examined whether LPBN moxonidine treatments change taste reactivity to hypertonic NaCl solution administered into the mouth by intra-oral (IO) cannula. Male Holtzman rats prepared with IO and bilateral LPBN cannulas received subcutaneous injections of furosemide (FURO; 10 mg/kg) and captopril (CAP; 5 mg/kg) to induce hypovolemia with mild hypotension and an accompanying salt appetite and thirst before testing the taste reactivity to oral infusions of 0.3 M NaCl (1.0 ml/min). In the first experiment 45 min after subcutaneous injections of FURO+CAP or vehicle, moxonidine was bilaterally injected into the LPBN, and then 15 min later both bodily and oral-facial ingestive and rejection responses to 0.3 M NaCl delivered through the IO cannula were assessed. Both LPBN vehicle and moxonidine treated rats showed increased ingestive and decreased rejection responses to the IO hypertonic solution. The IO 0.3 M NaCl infusion-evoked ingestive and rejection taste related behaviors were comparable in the LPBN vehicle- vs. the LPBN moxonidine-injected groups. In a second experiment, rats received the same FURO+CAP treatments and LPBN injections. However, beginning 15 min after the LPBN injections, they were given access to water and 0.3M NaCl and were allowed to consume the fluids for most of the next 60 min with the free access intake being interrupted only for a few minutes at 15, 30 and 60 min after the fluids became available. During each of these three brief periods, a taste reactivity test was conducted. On the three taste reactivity tests rats that received LPBN vehicle injections showed progressive declines in ingestive responses and gradual increases in rejection responses. However, in contrast to the LPBN vehicle treated rats, animals receiving bilateral injections of LPBN moxonidine maintained a high number of ingestive responses and a low number of rejection responses throughout the test period even in spite of evidencing substantial water and 0.3 M NaCl consumption during the periods of free access. The results suggest that after α2-adrenoceptor agonist delivery to the LPBN the acceptance of 0.3 M NaCl is sustained and the negative attributes of the solution are minimized. The maintained positive rewarding qualities of 0.3 M NaCl are likely to account for why LPBN moxonidine treated rats show such a remarkable salt appetite when assayed by the volume of hypertonic 0.3 M NaCl consumed.

Purinergic mechanisms of lateral parabrachial nucleus facilitate sodium depletion-induced NaCl intake.

Purinergic receptors are present in the lateral parabrachial nucleus (LPBN), a pontine structure involved in the control of sodium intake. In the present study, we investigated the effects of α,ß-methyleneadenosine 5'-triphosphate (α,ß-methylene ATP, selective P2X purinergic agonist) alone or combined with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2X purinergic antagonist) or suramin (non-selective P2 purinergic antagonist) injected into the LPBN on sodium depletion-induced 1.8% NaCl intake. Male Holtzman rats with stainless steel cannulas implanted into the LPBN were used. Sodium depletion was induced by treating rats with the diuretic furosemide (20mg/kg of body weight) followed by 24h of sodium-deficient diet. Bilateral injections of α,ß-methylene ATP (2.0 and 4.0nmol/0.2µl) into the LPBN increased sodium depletion-induced 1.8% NaCl intake (25.3±0.8 and 26.5±0.9ml/120min, respectively, vs. saline: 15.2±1.3ml/120min). PPADS (4nmol/0.2µl) alone into the LPBN did not change 1.8% NaCl intake, however, pretreatment with PPADS into the LPBN abolished the effects of α,ß-methylene ATP on 1.8% NaCl intake (16.9±0.9ml/120min). Suramin (2.0nmol/0.2µl) alone into the LPBN reduced sodium depletion-induced 1.8% NaCl intake (5.7±1.9ml/120min, vs. saline: 15.5±1.1ml/120min), without changing 2% sucrose intake or 24h water deprivation-induced water intake. The combination of suramin and α,ß-methylene ATP into the LPBN produced no change of 1.8% NaCl intake (15.2±1.2ml/120min). The results suggest that purinergic P2 receptor activation in the LPBN facilitates NaCl intake, probably by restraining LPBN mechanisms that inhibit sodium intake.

Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice.

Sickness behaviour appears to be the expression of a central motivational state that reorganises the organism's priorities to cope with infectious pathogens. To evaluate the possible participation of prostaglandins in lipopolysaccharide-induced sickness behaviours, mice were submitted to the tail suspension test (TST), forced swim test (FST), open field test and dark-light box test. Lipopolysaccharide (LPS, 100microg/kg; i.p.) administration increased the time spent immobile in the TST, increased the time spent floating in the FST, and depressed locomotor activity in the open field. Indeed, treatment with LPS decreased the total number of transitions made between the dark and light compartments of the apparatus. Pretreatment with indomethacin (10mg/kg; i.p.) or nimesulide (5mg/kg) blocked behavioural changes induced by LPS in the FTS, TST, open field and light-dark box test. This effect was similar to pretreatment with dexamethasone (1mg/kg), which is a steroidal drug that inhibits immune and inflammatory responses, including cytokine production. These findings confirm previous observations that have reported LPS-induced sickness behaviours. In addition, they provide evidence that the synthesis of prostaglandins is necessary for changes in depressive-like and exploratory behaviours in mice, which is supported by the fact that COX inhibitors also attenuate LPS-induced behavioural changes.

Lesions in the central amygdala impair sodium intake induced by the blockade of the lateral parabrachial nucleus.

The blockade of the lateral parabrachial nucleus (LPBN) with the GABAergic receptor agonist muscimol induces strong hypertonic NaCl intake in satiated and normovolemic rats, whereas lesions of the central nucleus of the amygdala (CeA) reduce sodium intake induced by different protocols. In the present study we investigated the effects of bilateral lesions of the CeA on water and 0.3M NaCl intake induced by GABAergic receptor activation with bilateral injections of muscimol into the LPBN in satiated rats. Male Holtzman rats (n=6-10) with bilateral sham or electrolytic lesions (2mA; 10s) of the CeA and stainless steel cannulas implanted bilaterally in the LPBN were used. Bilateral injections of muscimol (0.5nmol/0.2microl) into the LPBN in satiated sham-lesioned rats induced 0.3M NaCl intake (16.1+/-5.4ml/4h, vs. saline: 1.3+/-0.5ml/4h) and water intake (8.1+/-3.5ml/4h, vs. saline: 1.6+/-0.5ml/4h). Bilateral lesions of the CeA (3days) abolished 0.3M NaCl intake (0.1+/-0.1ml/4h) and water intake (0.1+/-0.1ml/4h) induced by bilateral injections of muscimol into the LPBN in satiated rats. The present results show that water and 0.3M NaCl intake induced by the blockade of LPBN neurons with muscimol depends on the integrity of the CeA, suggesting that facilitatory mechanisms present in the CeA are essential for water and hypertonic NaCl intake that arises after the blockade of the inhibitory mechanisms of the LPBN with muscimol.

Involvement of central alpha1-adrenoceptors on renal responses to central moxonidine and alpha-methylnoradrenaline.

Moxonidine (alpha2-adrenoceptor/imidazoline receptor agonist) injected into the lateral ventricle induces diuresis, natriuresis and renal vasodilation. Moxonidine-induced diuresis and natriuresis depend on central imidazoline receptors, while central alpha1-adrenoceptors are involved in renal vasodilation. However, the involvement of central alpha1-adrenoceptors on diuresis and natriuresis to central moxonidine was not investigated yet. In the present study, the effects of moxonidine, alpha-methylnoradrenaline (alpha2-adrenoceptor agonist) or phenylephrine (alpha1-adrenoceptor agonist) alone or combined with previous injections of prazosin (alpha1-adrenoceptor antagonist), yohimbine or RX 821002 (alpha2-adrenoceptor antagonists) intracerebroventricularly (i.c.v.) on urinary sodium, potassium and volume were investigated. Male Holtzman rats (n = 5-18/group) with stainless steel cannula implanted into the lateral ventricle and submitted to gastric water load (10% of body weight) were used. Injections of moxonidine (20 nmol) or alpha-methylnoradrenaline (80 nmol) i.c.v. induced natriuresis (196 +/- 25 and 171 +/- 30, respectively, vs. vehicle: 101 +/- 9 microEq/2 h) and diuresis (9.0 +/- 0.4 and 12.3 +/- 1.6, respectively, vs. vehicle: 5.2 +/- 0.5 ml/2 h). Pre-treatment with prazosin (320 nmol) i.c.v. abolished the natriuresis (23 +/- 4 and 76 +/- 11 microEq/2 h, respectively) and diuresis (5 +/- 1 and 7.6 +/- 0.8 ml/2 h, respectively) produced by i.c.v. moxonidine or alpha-methylnoradrenaline. RX 821002 (320 nmol) i.c.v. abolished the natriuretic effect of alpha-methylnoradrenaline, however, yohimbine (320 nmol) did not change renal responses to moxonidine. Phenylephrine (80 nmol) i.c.v. induced natriuresis and kaliuresis that were blocked by prazosin. Therefore, the present data suggest that moxonidine and alpha-methylnoradrenaline acting on central imidazoline receptors and alpha2-adrenoceptors, respectively, activate central alpha1-adrenergic mechanisms to increase renal excretion.

Enhancement of meal-associated hypertonic NaCl intake by moxonidine into the lateral parabrachial nucleus.

alpha2-Adrenoceptor activation with moxonidine (alpha2-adrenergic/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) enhances angiotensin II/hypovolaemia-induced sodium intake and drives cell dehydrated rats to ingest hypertonic sodium solution besides water. Angiotensin II and osmotic signals are suggested to stimulate meal-induced water intake. Therefore, in the present study we investigated the effects of bilateral injections of moxonidine into the LPBN on food deprivation-induced food intake and on meal-associated water and 0.3M NaCl intake. Male Holtzman rats with cannulas implanted bilaterally into the LPBN were submitted to 14 or 24h of food deprivation with water and 0.3M NaCl available (n=6-14). Bilateral injections of moxonidine (0.5nmol/0.2microl) into the LPBN increased meal-associated 0.3M NaCl intake (11.4+/-3.0ml/120min versus vehicle: 2.2+/-0.9ml/120min), without changing food intake (11.1+/-1.2g/120min versus vehicle: 11.2+/-0.9g/120min) or water intake (10.2+/-1.5ml/120min versus vehicle: 10.4+/-1.2ml/120min) by 24h food deprived rats. When no food was available during the test, moxonidine (0.5nmol) into the LPBN of 24h food-deprived rats produced no change in 0.3M NaCl intake (1.0+/-0.6ml/120min versus vehicle: 1.8+/-1.1ml/120min), nor in water intake (0.2+/-0.1ml/120min versus vehicle: 0.6+/-0.3ml/120min). The results suggest that signals generated during a meal, like dehydration, for example, not hunger, induce hypertonic NaCl intake when moxonidine is acting in the LPBN. Thus, activation of LPBN inhibitory mechanisms seems necessary to restrain sodium intake during a meal.

Involvement of forebrain imidazoline and alpha(2)-adrenergic receptors in the antidipsogenic response to moxonidine.

We investigated the participation of central alpha(2)-adrenoceptors and imidazoline receptors in the inhibition of water deprivation-induced water intake in rats. The alpha(2)-adrenoceptor and imidazoline antagonist idazoxan (320 nmol), but not the alpha(2)-adrenoceptor antagonist yohimbine, abolished the antidipsogenic effect of moxonidine (alpha(2)-adrenoceptor and imidazoline agonist, 20 nmol) microinjected into the medial septal area. Yohimbine abolished the antidipsogenic effect of moxonidine intracerebroventricularly. Therefore, central moxonidine may inhibit water intake acting independently on both imidazoline receptors and alpha(2)-adrenoceptors at different forebrain sites.