Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

In this study we investigated the effects of the injection into the supraoptic nucleus (SON) of non-peptide AT1- and AT2-angiotensin II (ANG II) receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP) receptor antagonist d(CH2)5-Tyr(Me)-AVP, on water and 3% NaCl intake induced by the injection of ANG II into the medial septal area (MSA). The effects on water or 3% NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 µl over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65%, N = 10, P<0.01) and sodium intake (81%, N = 8, P<0.01) induced by the injection of ANG II (10 nmol) into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. on the other hand, while there was a decrease in water intake (45%, N = 9, P<0.01), ANG II-induced sodium intake was significantly increased (70%, N = 8, P<0.01) following injection of the V1-type vasopressin antagonist d(CH2)5-Tyr(Me)-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses.

FURO/CAP: A protocol for sodium intake sensitization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride and sucrose intake in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of serotonergic 5-HT1A and oxytocinergic receptors of the lateral septal area in sodium intake regulation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration

We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t) SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e. g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EHrats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.

Cardiovascular responses to hydrogen peroxide into the nucleus tractus solitarius

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reproductive and sexual behavior changes in male rats exposed perinatally to picrotoxin

Previous studies in rats suggested that picrotoxin, a GABA(A) receptor antagonist, may cause long-term changes in male reproductive physiology and behavior in rats exposed during prenatal and postnatal periods. The present study has further examined this phenomenon. Wistar rat dams were dosed subcutaneously with 0.75 mg/kg picrotoxin in saline, or vehicle alone, during the perinatal period (day 19 of gestation, immediately after parturition, and once a day during the first 5 days of lactation). Birth weight and sexual maturation of pups were unchanged; however, plasma testosterone levels and sexual behavior was altered in male offspring. Although fertile, these males showed altered mating behavior in terms of a decrease in the mean number of mounts during a 30-min observation period with normal females. Some showed homosexual behavior when castrated and pretreated with exogenous estrogen. These findings suggest that perinatal exposure to picrotoxin alters sexual dimorphism in the developing rat brain, manifesting as altered reproductive performance and sexual behavior of males. (c) 2004 Elsevier B.V. All rights reserved.

The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphologic and Pharmacological Investigations in the Epicatechin Gastroprotective Effect

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Angiotensin II, progesterone, and prostaglandins are sequential steps in the pathway to bovine oocyte nuclear maturation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Aldosterone is not Involved in the Ventricular Remodeling Process Induced by Tobacco Smoke Exposure

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Serotonergic mechanisms of the lateral parabrachial nucleus in renal and hormonal responses to isotonic blood volume expansion

This study investigated the involvement of serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) in the control of sodium (Na+) excretion, potassium (K+) excretion, and urinary volume in unanesthetized rats subjected to acute isotonic blood volume expansion (0.15 M NaCl, 2 ml/100 g of body wt over 1 min) or control rats. Plasma oxytocin (OT), vasopressin (VP), and atrial natriuretic peptide (ANP) levels were also determined in the same protocol. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In rats treated with vehicle in the LPBN, blood volume expansion increased urinary volume, Na+ and K+ excretion, and also plasma ANP and OT. Bilateral injections of serotonergic receptor antagonist methysergide (1 or 4 mu g/200 eta 1) into the LPBN reduced the effects of blood volume expansion on increased Na+ and K+ excretion and urinary volume, while LPBN injections of serotonergic 5-HT2a/HT2c receptor agonist, 2.5-dimetoxi-4-iodoamphetamine hydrobromide (DOI;1 or 5 mu g/200 eta 1) enhanced the effects of blood volume expansion on Na+ and K+ excretion and urinary volume. Methysergide (4 mu g) into the LPBN decreased the effects of blood volume expansion on plasma ANP and OT, while DOI (5 mu g) increased them. The present results suggest the involvement of LPBN serotonergic mechanisms in the regulation of urinary sodium, potassium and water excretion, and hormonal responses to acute isotonic blood volume expansion.

Use of the elevated T-maze to study anxiety in mice

We have recently suggested that the elevated T-maze (ETM) is not a useful test to study different types of anxiety in mice if a procedure similar to that originally validated for rats is employed. The present study investigated whether procedural (five exposures in the enclosed arm instead of three as originally described for rats) and structural (transparent walls instead of opaque walls) changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and low escape latencies in mice. Results showed that five exposures to the ETM provoked consistent IAA, an effect that was independent of the ETM used. However, the ETM with transparent walls (ETMt) seemed to be more suitable for the study of conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA (low baseline latency with a gradual increase over subsequent exposures) and escape (low latency) profiles rendered it sensitive to the effects of anxiolytic and anxiogenic drugs. In addition to evaluation of drug effects on IAA and escape, the number of line crossings in the apparatus were used to control for locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05-0.1 mg/kg) and the 5-HT2B/2C receptor antagonist, SER 082 (0.5-2.0 mg/kg) failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT2B/2C receptor agonist, facilitated IAA but did not alter escape latency. Neither antidepressant utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10 mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively affect IAA, although caffeine did impair escape latencies. Present results suggest the ETMt is useful for the study of conditioned anxiety in mice. However, upon proximal threats (e.g. open arm exposure), mice do not exhibit escape behavior as an immediate defensive strategy, suggesting that latency to leave open arm is not a useful parameter to evaluate unconditioned fear in this species. (C) 2003 Elsevier B.V. All rights reserved.

Lateral parabrachial nucleus and serotonergic mechanisms in the control of salt appetite in rats

This study investigated the effects of bilateral injections of serotonergic receptor agonist and antagonist into the lateral parabrachial nucleus (LPBN) on the ingestion of water and 0.3 M NaCl induced by intracerebroventricular angiotensin II (ANG II) or by combined subcutaneous injections of the diuretic furosemide (Furo) and the angiotensin-converting enzyme inhibitor captopril (Cap). Rats had stainless steel cannulas implanted bilaterally into the LPBN and into the left lateral ventricle. Bilateral LPBN pretreatment with the serotonergic 5-HT1/5-HT2 receptor antagonist methysergide (4 mu g/200 nl each site) increased 0.3 M NaCl and water intakes induced by intracerebroventricular ANG II (50 ng/mu l) and 0.3 M NaCl intake induced by subcutaneous Furo + Cap. Pretreatment with bilateral LPBN injections of a serotonergic 5-HT2A/2C receptor agonist DOI (5 mu g/200 nl) significantly reduced 0.3 M NaCl intake induced by subcutaneous Furo + Cap. Pretreatment with methysergide or DOI into the LPBN produced no significant changes in the water intake induced by subcutaneous Furo + Cap. These results suggest that serotonergic mechanisms associated with the LPBN may have inhibitory roles in water and sodium ingestion in rats.