Involvement of V1-type vasopressin receptors on NaCl intake by hyperosmotic rats treated with muscimol in the lateral parabrachial nucleus.

GABAA receptor activation with agonist muscimol in the lateral parabrachial nucleus (LPBN) induces 0.3 M NaCl intake. In the present study, we investigated water and 0.3 M NaCl intake in male adult rats treated with losartan (angiotensin AT1 receptor antagonist) or MeT-AVP (V1-type vasopressin receptor antagonist) combined with muscimol or methysergide (5-HT2 antagonist) into the LPBN in rats treated with intragastric 2 M NaCl. After 2 M NaCl load and bilateral injections of muscimol (0.5 nmol/0.2 µL) into the LPBN, rats ingested water and 0.3 M NaCl. The pre-treatment of the LPBN with MeT-AVP (1 nmol/0.2 µL) but not losartan (50 µg/0.2 µL) in muscimol treated rats reduced 0.3 M NaCl intake. The pre-treatment of the LPBN with MeT-AVP did not modify the increased 0.3 M NaCl intake in rats treated with methysergide (4 µg/0.2 µL), suggesting that the effect of MeT-AVP was not due to non-specific inhibition of ingestive behavior. The results suggest that endogenous vasopressin in the LPBN facilitates the effects of GABAergic activation driving cell-dehydrated male rats to ingest 0.3 M NaCl.

Periodontal disease reduces water and sodium intake induced by injection of muscimol into the lateral parabrachial nucleus.

OBJECTIVE: Gamma-aminobutyric acid A (GABAA) receptor activation with muscimol in the lateral parabrachial nucleus (LPBN) induces water and 0.3M NaCl intake. The purpose of this study was to investigate whether a local inflammatory event, such as periodontal disease (PD), is able to alter the effects of muscimol on water and 0.3M NaCl intake in fluid-replete rats and in rats treated with furosemide (FURO) combined with captopril (CAP) injected subcutaneously. DESIGN: Male Wistar rats were divided into two groups: with PD and those without PD (control condition). Fifteen days after PD, both groups had cannulas implanted bilaterally into the LPBN. RESULTS: In fluid-replete rats without PD, injections of muscimol (0.5nmol/0.2µl) into the LPBN induced 0.3M NaCl and water intake and a pressor response. In fluid-replete rats with PD, a decrease was observed in water intake and pressor response but not in 0.3M NaCl intake. In control rats with FURO+CAP treatment, injections of muscimol into the LPBN increased 0.3M NaCl and water intake. In PD rats with FURO+CAP treatment, a decrease was observed in 0.3M NaCl and water intake after muscimol in the LPBN. Alveolar bone loss and interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) plasmatic concentration were higher in PD rats in comparison with controls. CONCLUSION: These results suggest that PD is able to reduce the pressor response and the dipsogenic and natriorexigenic effects induced by the activation of GABAA receptors in the LPBN, probably due to the elevation of the plasmatic concentration of pro-inflammatory cytokines IL-6 and TNF-α.

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride intake during cell dehydration.

BACKGROUND: Activation of GABA(B) receptors with baclofen into the lateral parabrachial nucleus (LPBN) induces ingestion of water and 0.3 M NaCl in fluid replete rats. However, up to now, no study has investigated the effects of baclofen injected alone or combined with GABA(B) receptor antagonist into the LPBN on water and 0.3 M NaCl intake in rats with increased plasma osmolarity (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. RESULTS: In fluid replete rats, baclofen (0.5 nmol/0.2 µl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (14.3 ± 4.1 vs. saline: 0.2 ± 0.2 ml/210 min) and water (7.1 ± 2.9 vs. saline: 0.6 ± 0.5 ml/210 min). In cell-dehydrated rats, bilateral injections of baclofen (0.5 and 1.0 nmol/0.2 µl) into the LPBN induced an increase of 0.3 M NaCl intake (15.6 ± 5.7 and 21.5 ± 3.5 ml/210 min, respectively, vs. saline: 1.7 ± 0.8 ml/210 min) and an early inhibition of water intake (3.5 ± 1.4 and 6.7 ± 2.1 ml/150 min, respectively, vs. saline: 9.2 ± 1.4 ml/150 min). The pretreatment of the LPBN with 2-hydroxysaclofen (GABA(B) antagonist, 5 nmol/0.2 µl) potentiated the effect of baclofen on 0.3 M NaCl intake in the first 90 min of test and did not modify the inhibition of water intake induced by baclofen in cell-dehydrated rats. Baclofen injected into the LPBN did not affect blood pressure and heart rate. CONCLUSIONS: Thus, injection of baclofen into the LPBN in cell-dehydrated rats induced ingestion of 0.3 M NaCl and inhibition of water intake, suggesting that even in a hyperosmotic situation, the blockade of LPBN inhibitory mechanisms with baclofen is enough to drive rats to drink hypertonic NaCl, an effect independent of changes in blood pressure.

AT1 receptor blockade in the lateral parabrachial nucleus reduces the effects of muscimol on sodium intake.

The blockade of the lateral parabrachial nucleus (LPBN) with GABA(A) receptor agonist muscimol induces robust hypertonic NaCl and water intake by rats. In the present study we investigated the effects of previous injections of losartan (AT(1) angiotensin receptor antagonist) into the LPBN on 0.3M NaCl and water intake induced by muscimol injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of muscimol (0.5 nmol/0.2 µl, n=8) into the LPBN in fluid replete rats induced 0.3M NaCl intake (23.4±4.1 vs. saline: 0.4±0.4 ml/3h) and water intake (9.3±1.9 vs. saline: 0.7±0.4 ml/3h) and pre-treatment of the LPBN with losartan (50 µg/0.2 µl) reduced 0.3M NaCl intake (3.3±2.5 ml/3h) and water intake (4.0±2.9 ml/3h) induced by muscimol. In rats treated with furosemide+captopril, pre-treatment with losartan into the LPBN attenuated the increase of 0.3M NaCl intake produced by muscimol (12.8±5.3, vs. saline+muscimol: 36.7±6.7 ml/3h) without changing water intake. Therefore, the results suggest that deactivation of LPBN inhibitory mechanisms by muscimol injections into the LPBN is facilitated by endogenous angiotensin II acting on AT(1) receptors in the LPBN, which drives rats to ingest large amounts of hypertonic NaCl.

GABAergic mechanisms of the lateral parabrachial nucleus on sodium appetite.

GABAergic activation in the lateral parabrachial nucleus (LPBN) induces sodium and water intake in satiated and normovolemic rats. In the present study we investigated the effects of GABAA receptor activation in the LPBN on 0.3M NaCl, water, 2% sucrose and food intake in rats submitted to sodium depletion (treatment with the diuretic furosemide subcutaneously+sodium deficient food for 24h), 24h food deprivation or 24 h water deprivation. Male Holtzman rats with bilateral stainless steel cannulas implanted into the LPBN were used. In sodium depleted rats, muscimol (GABAA receptor agonist, 0.5 nmol/0.2 microl), bilaterally injected into the LPBN, produced an inconsistent increase of water intake and two opposite effects on 0.3M NaCl intake: an early inhibition (4.3+/-2.7 versus saline: 14.4+/-1.0 ml/15 min) and a late facilitation (37.6+/-2.7 versus saline: 21.1+/-0.9 ml/180 min). The pretreatment of the LPBN with bicuculline (GABAA receptor antagonist, 1.6 nmol) abolished these effects of muscimol. Muscimol into the LPBN also reduced food deprivation-induced food intake in the first 30 min of test (1.7+/-0.6g versus saline: 4.1+/-0.6g), without changing water deprivation-induced water intake or 2% sucrose intake in sodium depleted rats. Therefore, although GABAA receptors in the LPBN are not tonically involved in the control of sodium depletion-induced sodium intake, GABAA receptor activation in the LPBN produces an early inhibition and a late facilitation of sodium depletion-induced sodium intake. GABAA activation in the LPBN also inhibits food intake, while it consistently increases only sodium intake and not water, food or sucrose intake.