Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis.

Graded doses of 50% ethanolic extract of dried fruit pulp of Aegle marmelos (AME) (100, 200 and 400 mg/kg) daily for 14 days in acetic acid (AA)-induced colitis in rats showed 200 mg/kg of AME as an optimal effective dose against AA-induced colonic damage score and weight. This dose (200 mg/kg; po) was further studied in AA-induced colitis for its effects on various physical (mucous/blood in stool, food and water intake and body weight changes), histology, antibacterial activity and biochemical parameters like free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase (acute-inflammatory marker) activities in rat colonic tissue. AME decreased colonic mucosal damage and inflammation (macroscopic and microscopic), mucous/bloody diarrhea, fecal frequency and increased body weight affected in AA-induced colitis. AME showed significant antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities thereby decreasing tissue damage and inflammation and thus, affording ulcer healing. The above effects of A. marmelos authenticated its use in indigenous system of Medicine.

The effect of melanocortin (Mc3 and Mc4) antagonists on serotonin-induced food and water intake of broiler cockerels

The current study was designed to examine the effects of intracerebroventricular injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment 1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 microg serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being injected with 10 microg serotonin. For Experiment 3, the chickens were given 10 microg serotonin after receiving 2 nmol MCL0020, and the level of food and water intake was determined 3 h post-injection. Results of this study showed that serotonin decreased food intake but increased water intake among the FD24 broiler cockerels and that these effects occurred in a dose-dependent manner. The inhibitory effect of serotonin on food intake was significantly attenuated by pretreatment with SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake was not altered by this pretreatment. These results suggest that serotonin hypophagia and hyperdipsia were mediated by different mechanisms in the central nervous system, and that serotonin required downstream activation of McRs to promote hypophagia but not hyperdipsia in the FD24 chickens.

Effect of L-5-Hydroxytryptophan on drinking behavior in Coturnix japonica (Temminck and Schlegel, 1849) (Galliformes: Aves): involvement of renin-angiotensin system

The purpose of this study was to explore the role of L-5-hydroxytryptophan (L-HTP) and its relationship with the renin-angiotensin system (RAS) on the drinking behavior in Japanese quails. Normally-hydrated quails that received injections of L-HTP (12.5; 25 and 50 mg.kg-1) by the intracoelomic route (ic) expressed an increase in water intake, which was inhibited by captopril, an angiotensin converting enzyme (ACE) inhibitor. In addition, captopril also induced such a response in birds under previous fluid deprivation. High doses of captopril (35-70 mg.kg-1, sc) in normally-hydrated quails decreased the spontaneous water intake while low doses of captopril (2-5 mg.kg-1, sc) did not prompt water intake after L-HTP administration. Losartan, an AT1 receptor antagonist in mammals, did not change the water intake levels in normally-hydrated or water-deprivated birds. Serotonin (5-HT) injections did not provoke its known dipsogenic response.

O objetivo deste estudo foi investigar a influência do L-5-hidroxitriptofano (L-HTP) e sua relação com o sistema renina-angiotensina (SRA) no comportamento dipsogênico de codornas. Codornas normohidratadas que receberam L-HTP em diferentes doses (12,5; 25 e 50 mg.kg-1) por via intracelomática (ic) expressaram um aumento na ingestão de água, o qual foi suprimido pela administração prévia de captopril (inibidor da ECA-enzima conversora de angiotensina). Esta ação inibitória do captopril, em menor intensidade, foi também evidenciada em aves previamente submetidas ao jejum hídrico. O tratamento isolado com captopril (35-70 mg.kg-1) reduziu consideravelmente a ingestão espontânea de água em codornas normohidratadas, enquanto baixas doses (2-5 mg.kg-1) não provocaram aumento na ingestão de água induzida pelo L-HTP. Losartan, um antagonista de receptores AT1 em mamíferos, não foi capaz de modificar os níveis de ingestão hídrica, tanto em aves normohidratadas quanto em aves privadas de água. Serotonina aplicada perifericamente não promoveu a conhecida resposta dipsogênica de mamíferos.

Mineralocorticoid modulation of central angiotensin-induced neuronal activity, water intake and sodium appetite

Central angiotensin II (AngII) stimulates water and salt solution intake. Pretreatment with low-dose mineralocorticoid (DOCA) enhances this AngII-induced intake of salt solutions (the synergy theory) in Wistar and Sprague Dawley rats but not in Fischer rats. This response is mediated via the AT-1 receptor. Electrophysiological experiments using iontophoretic application of AngII and the AT-1 receptor-specific non-peptide antagonist losartan showed excitation of neurons in the preoptic/medial septum region of urethane-anesthetized male Wistar rats. DOCA pretreatment further enhances this neuronal excitation in response to AngII and reduces the responses to losartan. This generated the hypothesis that DOCA-enhanced AngII-induced neuronal excitation is the neural support for the synergy theory. AT-2 receptors modulate these intake responses depending on sodium in the diet, and diuretic-induced dehydration during pregnancy produces a higher salt intake in the offspring. AngII-induced salt and water intakes were tested in offspring from Sprague Dawley mothers with only 1.8 percent NaCl to drink in which half were treated with furosemide. The important observations were a) the AT-1 antagonist alone suppressed intakes in offspring from mothers not treated with furosemide, b) both AT-1 and AT-2 antagonists suppressed intakes in offspring from furosemide-treated mothers, and c) combined administration of AT-1 and AT-2 antagonists greatly suppressed water intake in offspring from mothers not treated with furosemide. These results suggest that AT-1 and AT-2 receptors have variable properties (receptor number and/or second messengers). Furthermore, the activity and function of these central AngII receptors depend on the background mineralocorticoid levels. The exact mechanism of this influence, however, remains to be determined.

Modulation of feeding and drinking behaviour by catecholamines injected into nucleus accumbens in rats.

Nucleus accumbens is proposed as one of the centers in the neural circuitry involved in the regulation of feeding and drinking behaviour in rats. Injection of dopamine and angiotensin-II into this nucleus has been documented to affect water and food intake in rats. Reports on the effect of intracerebral injection of catecholamines on feeding and drinking behaviour in animal models are conflicting. Therefore, in the present study the effect of adrenaline and noradrenaline injected into nucleus accumbens on food and water intake in rats was assessed. 24 h basal food and water intakes were recorded in Wistar rats and were found to be 12.3 +/- 0.46 g and 21.7 +/- 1.03 ml respectively. Stainless steel cannulae were implanted stereotaxically into the nucleus accumbens. Four different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of adrenaline and noradrenaline were injected into the nucleus accumbens through the implanted cannulae in different group of animals and their 24 h food and water intakes were recorded following these injections. No change in food and water intake was observed following the administration of different doses of adrenaline. A significant increase in 24 h water intake reaching a maximum of 28.88 +/- 1.45 ml at 1 microgram dose, without change in food intake was observed following administration of different doses of noradrenaline. The noradrenaline-facilitated water intake was blocked when noradrenaline was injected following injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of nucleus accumbens resulted in a significant and sustained inhibition of water intake (16.61 +/- 0.67 ml) without change in food intake. These observations suggest that noradrenaline facilitates water intake without affecting food intake when injected into the nucleus accumbens in rats and the dipsogenic effect of noradrenaline is mediated by alpha-receptors. Adrenaline does not affect these ingestive behaviours when injected into the nucleus accumbens in rats.

Effect of injection of L-NAME on drinking response

The drinking behavior responses to centrally administered NG-nitro-L-arginine methyl ester (L-NAME; 10, 20 or 40 µg/µl), an inhibitor of nitric oxide synthase, were studied in satiated rats, with cannulae stereotaxically implanted into the lateral ventricle (LV) and subfornical organ (SFO). Water intake increased in all animals after angiotensin II (ANG II) injection into the LV, with values of 14.2 + or - 1.4 ml/h. After injection of L-NAME at doses of 10, 20 or 40 µg/µl into the SFO before injection of ANG II (12 ng/µl) into the LV, water intake decreased progressively and reached basal levels after treatment with 0.15 M NaCl and with the highest dose of L-NAME (i.e., 40 µg). The water intake obtained after 40 µg/µl L-NAME was 0.8 + or - 0.01 ml/h. Also, the injection of L-NAME, 10, 20 or 40 µg/µl, into the LV progressively reduced the water intake induced by hypertonic saline, with values of 5.3 + or - 0.8, 3.2 + or - 0.8 and 0.7 + or - 0.01 ml/h, respectively. These results indicate that nitric oxide is involved in the regulation of drinking behavior induced by centrally administered ANG II and cellular dehydration and that the nitric oxide of the SFO plays an important role in this regulation.

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1mul and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, O.15 M NaCl) into the 3rdV, water ingestion was 0.3 ñ 0.1 ml/h. Ramipril(l mug/mul)injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 ñ 0.2 ml/h). The injection of noradrenaline (40 nmol/mul) after isotonic saline induced an increase in water intake (3.0 ñ 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 + 0.3 ml/ h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.

Injection of ramipril into the lateral ventricle interferes with the drinking response induced by pharmacological and natural thirst stimuli

We investigated the effects of ramipril, an angiotensin I-converting enzyme (ACE) inhibitor, on water intake by male Holtzman rats (250-300 g) with cannulae implanted into the lateral ventricle. Intracerebroventricular (icv) injection of ramipril (1 µg/µl) significantly reduced drinking in response to subcutaneous (sc) injection of isoprenaline (100 µg/kg) from 8.49 + or - 0.69 to 2.96 + or - 0.36 ml/2 h, polyenthyleneglycol (PEG) (30 percent w/v, 10 ml/kg) from 9.51 + or - 2.20 to 1.6 + - 0.34 ml/2 h or water deprivation for 24 h from 12.61 + or - 0.83 to 5.10 + or - 1.37 ml/2 h. Ramipril had no effect on water intake induced by cellular dehydration produced by sc injection of hypertonic saline (2 M NaCl). These results are consistent with the hypothesis that ramipril acts as an ACE-blocking agent in the brain. The possibility that ramipril is transformed to ramiprilat, the active drug, by the brain is suggested

Acute effect of intracerebroventricular administration of zinc on the drinking behavior of rats induced by dehydration or central cholinergic and angiotensinergic stimulation

1. Zinc is a metal important for several biological functions including neuromodulation and neurotransmission in the central nervous system. 2. In the present paper we studied the acute effects of third ventricle injections (2 µl) of minute amounts of zinc acetate on the water intake of male, adult, Wistar rats (N = 7-14) under three conditions: water deprivation (14 h, overnight) and after third ventricle injections of carbachol (11 nmoles/rat in 2 µl) or angiotensin II (AII, 9.6 pmoles/rat in 2 µl). 3. Central injections of zinc acetate in different doses (0.3 and 3.0 nmoles/rat) induced a partial blockade of water intake of rats under all three conditions studied. Water intake after 120 min in control dehydrated rats (those receiving NaAc instead of Zn(Ac)2) was 7.89 + or - 0.47 ml while dehydrated animals receiving Zn(Ac)2 in the highest dose employed (3.0 nmoles/rat) animals receiving carbachol (2.41 + or - 0.84 ml). Angiotensin-treated animals exhibit a water intake of 3.85 + or - 0.48 ml after 45 min, a value reduced to 1.13 + or - 0.6 ml in those animals receiving angiotensin II plus zinc (3.0 nmoles/rat). 4. It is suggested that zinc alters the functional integrity of cholinergic and angiotensinergic systems in the central nervous system mediating water-intake behavior in rats

Anxiogenic activity of quinine--an experimental study in rodents.

Quinine, a cinchona alkaloid, was investigated for putative anxiogenic activity in view of clinical reports suggesting that it induces anxiety and apprehension following its use in malaria. The experimental paradigms chosen to elucidate anxiogenic activity have been shown to stand the tests of reliability and validity. Yohimbine, which has been shown to induce anxiety both in animals and in man, was used for comparison. Quinine was found to elicit a complex behavioural profile of activity ranging from overt central stimulation to marked central depression on dose increment. The doses 10 and 20 mg/kg, ip, of quinine chosen to investigate anxiogenic activity were comparable to those induced by 2.5 and 5 mg/kg ip of yohimbine. Quinine induced a dose-related anxiogenic activity in the open-field and elevated plus-maze tests in mice, and the social interaction and thirst conflict tests in rats, similar to effects induced by yohimbine. In addition, both quinine and yohimbine attenuated the effects of diazepam, an anxiolytic agent, in the open-field and thirst conflict tests. The results indicate that quinine exerts significant anxiogenic effect at a particular dose range.

Effect of chronic cadmium exposure on locomotor behaviour of rats.

Growing male rats were exposed to cadmium (Cd, 100 micrograms/kg, ip) for 51 days and the effect on the different components of locomotor behaviour was assessed on days 38, 46 and 51 of Cd exposure. Significant decrease in distance travelled, stereotypic time and movements, ambulatory time and vertical movements were observed in Cd-exposed rats, whereas the time of rest was increased. The number of entries into the inner as well as the outer squares and the total time spent in the inner squares of the floor area were significantly reduced. Results indicate that Cd exposure results in a general depression in all aspects of motor behaviour leading to decrease in gross locomotor activity. The involvement of an exaggerated emotional reactivity in the behavioural expression of the Cd-treated animals is also emphasized.