Sedation and need-free salt intake in rats treated with clonidine.

The effect of intraperitoneal injection of clonidine (9-72 microg/kg) on need-free 1.5% NaCl intake and on performance (defined as percent of a complete trial) in the rotarod test, was studied in normovolemic adult male rats. Clonidine (18 and 36 microg/kg) inhibited the 1.5% NaCl intake in a 2-h test at doses that did not alter the performance in the rotarod test. The dose of 36 microg/kg did not inhibit 10% sucrose intake. Only the highest dose (72 microg/kg) of clonidine inhibited the 1.5% NaCl intake and the performance in the rotarod test, and produced signs of sedation. Sedation was determined either by change in posture (immobility or lack of postural tonus) of the animals during the ingestive test or by their performance in the rotarod test. The results suggest that sedation is not a determinant effect on the inhibition of 1.5% NaCl intake induced by clonidine.

Central alpha-adrenergic agonists and need-induced 3% NaCl and water intake.

In the present study, noradrenaline (NOR, alpha-non-specific adrenergic agonist), clonidine (CLO, alpha 2), phenylephrine (PHE, alpha 1) or isoproterenol (ISO, beta-agonist) was injected in the medial septal area (MSA) of water-deprived, sodium-deplete or food-deprived rats. NOR (80, 160 nmol) inhibited the intake of 3% NaCl, water deprivation-induced and meal-associated water intake. Food deprivation-induced food intake and 10% sucrose intake were not altered by NOR. CLO (10, 20, 30, 40 nmol) inhibited (80-100% inhibition compared to control during 60 min) the intake of 3% NaCl, water deprivation-induced and meal-associated water intake. CLO had a weaker inhibition on food and 10% sucrose intake (30-50% less than the control during 60 and 15 min, respectively). PHE (160 nmol) inhibited 3% NaCl intake and 10% sucrose intake (30% less than the control for 15-30 min). ISO (160 nmol) did not alter water or 3% NaCl intake. NOR induced an increase, CLO and ISO induced a decrease, and PHE no alteration in mean arterial pressure. NOR did not alter water or 3% NaCl intake when injected unilaterally into the caudate nucleus. The results suggest that NOR injected in the MSA acts on alpha 2-adrenergic receptors inducing a specific inhibition of 3% NaCl and water intake.

Receptor-mediated effects of clonidine on need-induced 3% NaCl and water intake.

Clonidine combined with adrenergic antagonists were injected in the medial septal area in order to characterize the type of receptors involved with its inhibitory effect on 3% NaCl and water intake of sodium-depleted (furosemide + 24 h of removal of ambient sodium) and 30-h water-deprived rats, respectively. The inhibitory effect of clonidine (20 nmol) on need-induced water intake was reduced 50% by an 80-nmol dose of either idazoxan, yohimbine or prazosin. The inhibitory effect of clonidine (30 nmol) on need-induced 3% NaCl intake was completely antagonized by idazoxan (80, 160 nmol), not altered by yohimbine (40-160 nmol), and partially potentiated (40 nmol) or inhibited (160 nmol) by prazosin. Propranolol did not alter the effects of clonidine on either water (80 nmol) or 3% NaCl (40-160 nmol) intake. The results suggest that the inhibitory effects of clonidine on 3% NaCl and water intake are mediated by different types of alpha2-adrenergic receptors.

Antagonism of clonidine injected intracerebroventricularly in different models of salt intake.

Clonidine, an alpha 2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In th present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats. Clonidine injected intracerebroventricularly (i.c.v.) inhibited the 1.5% NaCl intake for 1209 min by 50 to 90% in every model tested. Therefore, different models of salt intake are inhibited by i.c.v. injection of clonidine. Idazoxan, an alpha 2-adrenergic antagonist, injected i.c.v. at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.

Antagonism of clonidine injected intracerebroventricularly in different models of salt intake

Clonidine, and alpha2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In the present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats. Clonidine injected intracerebroventricularly (icv) inhibited the 1.5 per cent NaCl intake for 120 min by 50 to 90 per cent in every model tested. Therefore, different models of salt intake are inhibited by icv injection of clonidine. Idazoxan, an alpha2-adrenergic antagonist, injected icv at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.

Antagonism of the renin-angiotensin system and water deprivation-induced NaCl intake in rats.

Adult male rats (n = 5-7 per group) were water deprived for 24 h with only food available. Then they had access to water for 2 h. At the end of the 2 h, 1.5% NaCl was offered to the animals and the intake was measured for another 2 h. The rats drank an average of 9.8 +/- 3.0 ml/120 min of 1.5% NaCl; water intake during this time was negligible (not more than 1.0 ml/120 min). Captopril injected i.p. at the doses of 12 and 24 mg/ kg induced 60-90% inhibition of the intake. Losartan or PD123319 injected i.c.v. induced 50-80% inhibition of the intake. Losartan (80 nmol) inhibited the intake at a lower dose than PD123319 (160 nmol). Neither losartan nor PD123319 inhibited 10% sucrose intake. The inhibition of 1.5% NaCl intake was not related to alterations in arterial pressure. The results show that the antagonism of the renin-angiotensin system inhibits the 1.5% NaCl intake induced by water deprivation. The inhibition induced by the angiotensin II antagonists suggest that this peptide is important for the control of salt intake induced by water deprivation.