Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally

We investigated the effect of L-NAME, a nitric oxide (NO) inhibitor and sodium nitroprusside (SNP), an NO-donating agent, on pilocarpine-induced alterations in salivary flow, mean arterial blood pressure (MAP) and heart rate (HR) in rats. Male Holtzman rats (250-300 g) were implanted with a stainless steel cannula directly into the median preoptic nucleus (MnPO). Pilocarpine (10, 20, 40, 80, 160 µg) injected into the MnPO induced an increase in salivary secretion (P<0.01). Pilocarpine (1, 2, 4, 8, 16 mg/kg) ip also increased salivary secretion (P<0.01). Injection of L-NAME (40 µg) into the MnPO prior to pilocarpine (10, 20, 40, 80, 160 µg) injected into the MnPO or ip (1, 2, 4, 8, 16 mg/kg) increased salivary secretion (P<0.01). SNP (30 µg) injected into the MnPO or ip prior to pilocarpine attenuated salivary secretion (P<0.01). Pilocarpine (40 µg) injection into the MnPO increased MAP and decreased HR (P<0.01). Pilocarpine (4 mg/kg body weight) ip produced a decrease in MAP and an increase in HR (P<0.01). Injection of L-NAME (40 µg) into the MnPO prior to pilocarpine potentiated the increase in MAP and reduced HR (P<0.01). SNP (30 µg) injected into the MnPO prior to pilocarpine attenuated (100%) the effect of pilocarpine on MAP, with no effect on HR. Administration of L-NAME (40 µg) into the MnPO potentiated the effect of pilocarpine injected ip. SNP (30 µg) injected into the MnPO attenuated the effect of ip pilocarpine on MAP and HR. The present study suggests that in the rat MnPO 1) NO is important for the effects of pilocarpine on salivary flow, and 2) pilocarpine interferes with blood pressure and HR (side effects of pilocarpine), that is attenuated by NO.

The compulsive-like aspect of the head dipping emission in rats with chronic electrolytic lesion in the area of the median raphe nucleus

Head dipping (HD) is a behavioral pattern considered to have a risk assessment or an exploratory role and is used as a complementary parameter to evaluate anxiety in experimental animals. Since rats with electrolytic lesion in the area of the median raphe nucleus displayed high frequencies of HD in a previous study, the present investigation was undertaken to confirm this observation and to determine its anxiety-related origin. HD episodes were counted in adult male Wistar rats (270-350 g) with electrolytic lesion (N = 11) and sham-lesioned controls (N = 12). When HD was measured for 60 min on an elevated open platform, lesioned rats emitted 13 times more HD than controls (264.7 ± 93.3 vs 20.3 ± 7.6 episodes), with the difference being statistically significant (P < 0.05). HD counts during 10-min sessions held 7, 14, 21, 27, and 63 days after lesion showed significantly higher means (range: 28.14 ± 5.38 to 62.85 ± 9.48) compared to sham-lesioned controls (range: 7.37 ± 1.13 to 8.5 ± 1.45). Normal rats stepped down into their home cages when the vertical distance between them and the cage was short (16 cm), and the step-down latencies increased with increasing depths (36.7 ± 7.92 to 185.87 ± 35.44 s). Lesioned rats showed a similar behavior when facing the shortest depth, but had a significantly increased number (23.28 ± 2.35 episodes) and latency (300 ± 0.00 s) of HD compared to normal rats (9.25 ± 1.37 episodes and 185.87 ± 35.44 s) when facing the greatest depth (30 cm). This suggests that HD may be a depth-measuring behavior related to risk assessment.

Associativismo e comportamento eleitoral na eleição de 2002

A autora analisa a participação eleitoral em 2002, relacionando-a às formas de participação associativa. A hipótese testada é de que o eleitor com vínculos associativos tem maior participação eleitoral. Nesse sentido, os resultados sugerem que para os eleitores ativos há um perfil associado à participação em greves e filiação sindical mas, quanto à sua filiação partidária, sugerem que há outros fatores intervenientes na relação. O artigo utiliza os dados do ESEB 2002

Efeito do lítio sobre a hiperatividade locomotora induzida pela lesão eletrolítica da região do núcleo mediano da rafe em ratos

A lesão do núcleo mediano da rafe (NMR) produz sintomas que sugerem validade de face ao episódio maníaco. Esta pesquisa avaliou o efeito do lítio sobre a hiperatividade locomotora induzida por esta lesão. Vinte e um ratos Wistar machos foram submetidos à lesão eletrolítica da região do NMR (LR) e 17 foram submetidos à lesão fictícia (LF). Após recuperação, a atividade locomotora foi avaliada na caixa de atividade (Med Associates/ENV-515). Parte dos animais destes grupos recebeu tratamentos com lítio (47,5 mg/kg/2x dia i.p.) por 10 dias, enquanto o restante foi tratado com salina no mesmo esquema. A reavaliação ao final dos tratamentos demonstrou que o lítio reduziu significantemente a atividade locomotora em relação à avaliação inicial no grupo LR (ANOVA/Bonferroni p < 0,05), tornando-a equivalente aos baixos níveis dos grupos LF. Estes dados sustentam a hipótese de que as manifestações induzidas pela lesão do NMR podem constituir um modelo animal de mania.

Anxiolytic-like effects of median raphe nucleus lesion in the elevated T-maze

The cell bodies of 5-HT containing neurons that innervate the limbic forebrain are mainly found in the dorsal raphe nucleus and in the median raphe nucleus (MRN). To assess the role of the median raphe nucleus in anxiety, rats bearing either electrolytic or 5-HT-selective neurotoxic lesion of the MRN were tested in the elevated T-maze. This apparatus consists of two opposed open arms perpendicular to one enclosed arm. Two tasks are performed in succession by the same rat in one experimental session, namely inhibitory avoidance of the open arm, taken as a measure of conditioned anxiety and one-way escape from the open arm, considered as a measure of unconditioned fear. The test was performed 7 days after the electrolytic lesion (3 mA, 10 s) or 14 days after the neurotoxic lesion (5,7-DHT, 8 mug/1 mul). The results showed that while the electrolytic lesion impaired both inhibitory avoidance and one-way escape, the neurotoxic lesion impaired only inhibitory avoidance. Therefore, serotonergic pathways originating in the MRN seem to participate in the modulation of conditioned anxiety but not unconditioned fear. Other neurotransmitter systems that either originate in or pass through the MRN may regulate unconditioned fear. (C) 2003 Elsevier B.V. All rights reserved.

THE ROLE OF ANGIOTENSIN AT1 RECEPTORS IN THE DIURETIC, NATRIURETIC, KALIURETIC AND BLOOD-PRESSURE RESPONSES INDUCED BY ANGIOTENSIN-II ACTIVATION OF THE MEDIAN PREOPTIC NUCLEUS IN CONSCIOUS RATS

We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar(1), Ala(8)]-ANG II and [Sar(1), Thr(8)]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT 1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was collected in rats submitted to a water load (5% body weight) by gastric gavage, followed by a second water load (5% body weight) 1 h later. The volume of the drug solutions injected was 0.5 mu l over 10-15 s. Pre-treatment with [Sar(1), Ala(8)]-ANG II (12 rats) and [Sar(1), Thr(8)]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/- 1.0 and 10.7 +/- 1.2, respectively), whereas losartan (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs 7.6 +/- 1.5) the urine excretion induced by injection of 12 ng of ANG II (14 rats). [Sar(1), Ala(8)]-ANG II impaired Na+ excretion (193 +/- 16 vs 120 +/- 19): whereas [Sar(1), Thr(8)]-ANG II and losartan blocked Na+ excretion (193 +/- 16 vs 77 +/- 15 and 100 +/- 12, respectively) induced by ANG II. Similar effects induced by ANG II on K+ excretion were observed with [Sar(1), Ala(8)]-ANG II, [Sar(1), Thr(8)]-ANG II, and losartan pretreatment (133 +/- 18 vs 108 +/- 11, 80 +/- 12, and 82 +/- 15, respectively). The same doses as above of [Sar(1), Ala(8)]-ANG II (8 rats), [Sar(1), Thr(8)]-ANG II (8 rats). and losartan (9 rats) blocked the increase in the arterial blood pressure induced by 12 ng of ANG II (12 rats) (32 +/- 4 ru 4 +/- 2, 3.5 +/- 1, and 2 +/- 1: respectively. The results indicate that the AT1 receptor subtype participates in the increases of diuresis, natriuresis. kaliuresis and arterial blood pressure induced by the administration of ANG II into the MnPO.

Role of 5-HT in stress, anxiety, and depression

There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphe nucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To study the role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5 HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in the T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/(2C)) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, the nonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.

Ibotenate lesion of the medial hypothalamus alters the salt intake and pressor responses to activation of the median preoptic nucleus in rats

We investigated the influence of ibotenic acid lesions of the medial hypothalamus (MH) on salt appetite and arterial blood pressure responses induced by angiotensinergic and adrenergic stimulation of the median preoptic nucleus (MnPO) of rats. Previous injection of the adrenergic agonists norepinephrine, clonidine, phenylephrine, and isoproterenol into the MnPO of sham MH-lesioned rats caused no change in the sodium intake induced by ANG II. ANG II injected into the MnPO of MH-lesioned rats increased sodium intake compared with sham-lesioned rats. Previous injection of clonidine and isoproterenol increased, whereas phenylephrine abolished the salt intake induced by ANG II into the MnPO of MH-lesioned rats. Previous injection of norepinephrine and clonidine into the MnPO of sham MH-lesioned rats caused no change in the mean arterial pressure (MAP) induced by ANG II. Under the same conditions, previous injection of phenylephrine increased, whereas isoproterenol reversed the increase in MAP induced by angiotensin II (ANG II). ANG II injected into the MnPO of MH-lesioned rats induce a decrease in MAP compared with sham-lesioned rats. Previous injection of phenylephrine or norepinephrine into the MnPO of MH-lesioned rats induced a negative MAP, whereas pretreatment with clonidine or isoproterenol increased the MAP produced by ANG II injected into the MnPO of sham- or MH-lesioned rats. These data show that ibotenic acid lesion of the MH increases the sodium intake and presser responses induced by the concomitant angiotensinergic, alpha(2) and beta adrenergic activation of the MnPO, whereas alpha(1) activation may have opposite effects. MH involvement in excitatory and inhibitory mechanisms related to sodium intake and MAP control is suggested.

Effect of ibotenate lesions of the ventromedial hypothalamus on the water and salt intake induced by activation of the median preoptic nucleus in sodium-depleted rats

In this study we investigated the influence of a ventromedial hypothalamus (VMH) lesion with ibotenic acid on water and sodium intake and presser responses induced by combined treatment of the median preoptic nucleus (MnPO) with angiotensin Il (ANG II) and adrenergic agonists (phenylephrine, norepinephrine, isoproterenol and clonidine). Male Holtzman rats with a stainless steel cannula implanted into the MnPO and bilateral sham (vehicle) or VMH lesions with ibotenic acid were used. The ingestion of water and sodium and mean arterial pressure (MAP) were determined in separate groups submitted to sodium depletion with the diuretic furosemide (20 mg/rat). ANG II (10 pmol) injection into the MnPO of sham-lesioned rats induced water and sodium intake and presser responses. VMH-lesion reduced ANG II-induced water intake and increased saline intake, In sham rats phenylephrine (80 nmol) into MnPO increased, whereas norepinephrine (80 nmol) and clonidine (40 nmol) reduced ANG II-induced water intake while sodium intake was reduced only by clonidine into MnPO. In VMH-lesioned rats, phenylephrine reduced, noradrenaline increased and clonidine produced no effect on ANG II-induced water intake. In lesioned rats ANG II-induced sodium intake was reduced by phenylephrine and noradrenaline, whereas clonidine produced no change. ANG II-induced presser response was reduced in VMH-lesioned rats, but the presser response combining ANG II and phenylephrine or noradrenaline in VMH-lesioned rats was bigger than sham rats. These results show that the VMH is important for the changes in water and sodium intake and cardiovascular responses induced by angiotensinergic and adrenergic activation of the MnPO. (C) 1997 Elsevier B.V. B.V.

GENETIC MECHANISMS FOR THE DEVELOPMENT OF REPRODUCTIVE-ORGANS OF APIS-MELLIFERA WORKERS AND DIPLOID DRONES - A COMPLEMENTARY HYPOTHESIS

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

Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors

Estrogen deficiency has been associated with stress, anxiety and depression. Estrogen receptors have been identified in the median raphe nucleus (MRN). This structure is the main source of serotonergic projections to the hippocampus, a forebrain area implicated in the regulation of defensive responses and in the resistance to chronic stress. There is evidence showing that estrogen modulates 5-HT1A receptor functions. In the MRN, somatodendritic 5-HT1A receptors control the activity of serotonergic neurones by negative feedback. The present study evaluated the effect of intra-MRN injection of estradiol benzoate (EB) (600 or 1200 ng/0.2 mu l) on the performance of ovariectomised rats submitted to the elevated plus-maze test of anxiety and to the open-field test. Additionally, the same effect was evaluated with a previous intra-MRN injection of WAY 100635 (100 ng/0.2 mu l), an antagonist of 5-HT1A receptors. The results showed that both doses of EB increased the percentage of entries and the percentage of time spent into the open arms, suggestive of an anxiolytic effect. The highest dose of the drug also increased the number of entries into the enclosed arm and locomotion in the open field, indicating a stimulatory motor effect. WAY 100635 antagonised the effect of estradiol in the elevated plus-maze and in the open-field. The results show that estrogen receptors of the MRN are implicated in the regulation of anxiety-related behaviour. The results also support claims that the effect of estrogen involves a change in 5-HT1A receptor function. (C) 2005 Elsevier B.V. All rights reserved.

EFFECT OF LATERAL HYPOTHALAMUS LESIONS ON THE WATER AND SALT INTAKE, AND SODIUM AND URINE EXCRETION INDUCED BY ACTIVATION OF THE MEDIAN PREOPTIC NUCLEUS IN CONSCIOUS RATS

In this-study we investigated the influence of electrolytic lesion of the lateral hypothalamus (LH) on the water and salt appetite, and the natriuretic, diuretic and cardiovascular effects induced by angiotensinergic, cholinergic and noradrenergic stimulation of the median preoptic nucleus (MnPO) in rats. Male Holtzman rats were implanted with a cannula into the MnPO. Other groups of sham- and LH-lesioned rats received a stainless steel cannula implanted into the MnPO. ANGII injection into the MnPO induced water and sodium intake, and natriuretic, diuretic, presser and tachycardic responses. Carbachol induced water intake, and natriuretic, presser and bradycardic responses, whereas noradrenaline increased urine, sodium excretion and blood pressure, and induced bradycardia. In rats submitted to LH-lesion only, water and sodium intake was reduced compared with sham rats. LH lesion also reduced the sodium ingestion induced by ANGII (12 ng) into the MnPO. In LH-lesioned rats, the dipsogenic, diuretic and presser responses induced by ANGII (12 ng), carbachol (2 nmol) and noradrenaline (20 nmol) injection into the MnPO were reduced. The same occurred with sodium excretion when carbachol (2 nmol) and noradrenaline (20 nmol) were injected into the MnPO of LH-lesioned rats, whereas ANGII(12 ng) induced an increase in sodium excretion. These data show that electrolytic lesion of the LH reduces fluid and sodium intake, and presser responses to angiotensinergic, cholinergic and noradrenergic activation of the MnPO. LH involvement with MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested.