EFFECT OF ELECTROLYTIC AND CHEMICAL LESION BY IBOTENIC ACID OF THE AMYGDALA ON SALT INTAKE

Sodium chloride intake was studied in male Holtzman rats weighing 250-300 g submitted to electrolytic and chemical lesion of the cell bodies, not fibers of the amygdaloid complex. Sodium chloride (1.5%) intake increased in animals with electrolytic lesion of the corticomedial nucleus of the amygdala. Sodium chloride (1.5%) intake increased after ibotenic acid injection into the corticomedial nucleus of the amygdala to a larger extent (26.6 +/- 9.2 to 147.6 +/- 34.6 ml/5 days). The results indicate that sodium intake response can be induced by lesions, which involved only cell bodies. The fibers of passage of the corticomedial nucleus of the amygdala produce a water intake less consistent than that induced by ibotenic acid, which is more acute. The results show that cell bodies of this region of the amygdala are involved in the control of sodium chloride intake.

Effect of chronic treatment with Clomipramine on food intake, macronutrient selection and body weight gain in rats

Long-term treatment with clomipramine (CMI), a tricyclic antidepressant, induces food craving and body weight gain in patients. The present study investigated the effects of chronic treatment with CMI on total food intake, macronutrient selection, and body weight gain in rats. Male Wistar rats were maintained on a dietary self-selection regime with separate sources of protein, fat and carbohydrate. Animals received i.p. injections of CMI (0, 3, 10, 30 mg/kg) during 27 consecutive days. Food consumption and body weight were recorded daily and results were calculated as average of three consecutive days, namely during pre-treatment (3 d before pharmacological treatment), treatment (7th-9th; l6th-l8th and 25th-27th days), and post-treatment (28th-33rd days). Results showed that CMI (30 mg/kg) significantly decreased energy intake during all treatment period, an effect that was related to a decrease in both carbohydrate-rich diet intake and body weight gain. At dose of 3 mg/kg CMI increased the total energy intake in the 16th-18th days, suggesting an apparent biphasic effect of chronic treatment with CMI on caloric intake. Chronic administration with CMI (27 d) did not alter protein-rich or fat-rich diet consumption. The main result of this study indicated that chronic treatment with CMI decreases rather than increase food consumption and body weight gain in rats exposed to a macronutrient self-selection procedure.

Inhibitory effect of DUP-753 on the drinking responses of rats to central administration of noradrenaline and angiotensin II and to dehydration

We investigated the effect of losartan (DUP-753) on the dipsogenic responses produced by intracerebroventricular (icv) injection of noradrenaline (40 nmol/mu l) and angiotensin II (ANG II) (2 ng/mu l) in male Holtzman rats weighing 250-300 g. The effect of DUP-753 was also studied in animals submitted to water deprivation for 30 h. After control injections of isotonic saline (0.15 M NaCl, 1 mu l) into the lateral ventricle (LV) the water intake was 0.2 +/- 0.01 ml/h. DUP-753 (50 nmol/mu l) when injected alone into the LV of satiated animals had no significant effect on drinking (0.4 +/- 0.02 ml/h) (N = 8). DUP-753 (50 nmol/mu l) injected into the LV prior to noradrenaline reduced the water intake from 2.4 +/- 0.8 to 0.8 +/- 0.2 ml/h (N = 8). The water intake induced by injection of ANG II and water deprivation was also reduced from 9.2 +/- 1.4 and 12.7 +/- 1.4 ml/h to 0.8 +/- 0.2 and 1.7 +/- 0.3 ml/h (N = 6 and N = 8), respectively. These data indicate a correlation between noradrenergic pathways and angiotensinergic receptors and lead us to conclude that noradrenaline-induced water intake may be due to the release of ANG II by the brain. The finding that water intake was reduced by DUP-753 in water-deprived animals suggests that dehydration releases ANG II, and that AT(1) receptors of the brain play an important role in the regulation of water intake induced by deprivation.

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 1 mu l 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, 0.15 M NaCl) into the 3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mu g/mu l) injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/mu l) after isotonic saline induced an increase in water intake (3.0 +/- 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.

Effects of subtypes alpha- and beta-adrenoceptors of the lateral hypothalamus on the water and sodium intake induced by angiotensin II injected into the subfornical organ

The present experiments were conducted to investigate the role of the alpha (1A)-, alpha (1B), beta (1),- and beta (2)-adrenoceptors of the lateral hypothalamus (LH) on the water and salt intake responses elicited by subfornical organ (SFO) injection of angiotensin II (ANG II) in rats. 5-methylurapidil (an alpha (1A)-adrenergic antagonist), cyclazosin (an alpha (1B)-adrenergic antagonist) and ICI-118,551 (a beta (2)-adrenergic antagonist) injected into the LH produced a dose-dependent reduction, whereas efaroxan (an alpha (2)-antagonist) increased the water intake induced by administration of ANG II into the SFO. These data show that injection of 5-methylurapidil into the LH prior to ANG II into the SFO increased the water and sodium intake induced by the injection of ANG II. The present data also show that atenolol (a beta (1)-adrenergic antagonist), ICI-118,551, cyclazosin, or efaroxan injected into the LH reduced in a dose-dependent manner the water and sodium intake to angiotensinergic activation of SFO. Thus, the alpha (1)- and beta -adrenoceptors of the LH are possibly involved with central mechanisms dependent on ANG II and SFO that control water and sodium intake. (C) 2000 Elsevier B.V. B.V. All rights reserved.

ROLE OF ADRENERGIC PATHWAYS OF THE MEDIAL PREOPTIC AREA IN ANGII-INDUCED WATER-INTAKE AND RENAL EXCRETION IN RATS

In this study, we investigated the participation of adrenergic neurotransmission in angiotensin II- (ANGII)-induced water intake and urinary electrolyte excretion by means of injection of the alpha(1)-, alpha(2)-, and beta-adrenoceptor antagonists and ANGII into the medial preoptic area (MPOA) in rats. Prazosin (an alpha(1)-adrenergic antagonist) antagonized the water ingestion, Na+, K+ and urine excretion induced by ANGII, whereas yohimbine (an alpha(2)-adrenergic antagonist) enhanced the Na+, K+ and urine excretion induced by ANGII. Propranolol (a nonselective beta-adrenoceptor blocker) antagonized the water ingestion and enhanced the Na+ and urine excretion induced by ANGII. Previous treatment with prazosin reduced the presser responses to ANGII, whereas yohimbine had opposite effects. Previous injection of propranolol produced no effects in the presser responses to ANGII. These results suggest that the adrenergic neurotransmission in the MPOA may actively participate in ANGII-induced dipsogenesis, natriuresis, kaliuresis and diuresis in a process that involves alpha(1)-, alpha(2)-, and beta-adrenoceptors.

ALPHA-ADRENERGIC PATHWAYS IN THE LATERAL HYPOTHALAMUS ARE IMPORTANT FOR THE DIPSOGENIC EFFECT OF CARBACHOL INJECTED INTO THE MEDIAL SEPTAL AREA

We studied the effect of the alpha(1)- and alpha(2)-adrenergic receptors of the lateral hypothalamus (LH) on the control of water intake induced by injection of carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300 g) implanted with chronic stainless steel cannulae into the LH and MSA. The volume of injection was always 1 mu l and was injected over a period of 30-60 s. For control, 0.15 M NaCl was used. Clonidine (20 nmol) but not phenylephrine (160 nmol) injected into the LH inhibited water intake induced by injection of carbachol (2 nmol) into the MSA, from 5.4 +/- 1.2 ml/h to 0.3 +/- 0.1 and 3.0 +/- 0.9 ml/h, respectively (N = 26). When we injected yohimbine (80 nmol) + clonidine (20 nmol) and prazosin (40 nmol) + clonidine (20 nmol) into theLH, water intake induced by injection of carbachol into the MSA was inhibited from 5.4 +/- 1.2 ml/h to 0.8 +/- 0.5 and 0.3 +/- 0.2 ml/h, respectively (N = 19). Water intake induced by carbachol (2 nmol) injected into the MSA was decreased by previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin (40 nmol) + phenylephrine (l60 nmol) from 5.4 +/- 1.2 ml/h to 1.0 +/- 0.7 and 1.8 +/- 0.8 ml/h, respectively (N = 16). The cannula reached both the medial septal area in its medial portion and the lateral hypothalamus. It has been suggested that the different pathways for induction of drinking converge on a final common pathway. Thus, adrenergic stimulation of alpha(2),-adrenoceptors ofLH can influence this final common pathway.