L. A. De Luca

Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats

In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

Serotonergic mechanism of the lateral parabrachial nucleus and relaxin-induced sodium intake

It has been shown that central or peripheral injections of the peptide relaxin induces water intake, not sodium intake in rats. Important inhibitory mechanisms involving serotonin and other neurotransmitters in the control of water and NaCl intake have been demonstrated in the lateral parabrachial nucleus (LPBN). In the present study, we investigated the effects of bilateral injections of methysergide (serotonergic receptor antagonist) into the LPBN on intracerebroventricular (i.c.v.) relaxin-induced water and NaCl intake in rats. Additionally, the effect of the blockade of central angiotensin AT(1) receptors with i.c.v. losartan on relaxin-induced water and NaCl intake in rats treated with methysergide into the LPBN was also investigated. Male Holtzman rats with cannulas implanted into the lateral ventricle (LV) and bilaterally in the LPBN were used. Intracerebroventricular injections of relaxin (500 ng/1 microl) induced water intake (5.1+/-0.7 ml/120 min), but not significant 1.8% NaCl intake (0.5+/-0.4 ml/120 min). Bilateral injections of methysergide (4 microg/0.2 microl) into the LPBN strongly stimulated relaxin-induced 1.8% NaCl intake (34.5+/-10.9 ml/120 min) and slightly increased water intake (10.5+/-4.9 ml/120 min). The pretreatment with i.c.v. losartan (100 microg/1 microl) abolished the effects of i.c.v. relaxin combined with LPBN methysergide on 1.8% NaCl intake (0.5+/-0.4 ml/120 min). Losartan (100 microg/1 microl) also abolished relaxin-induced water intake in rats injected with methysergide into the LPBN (1.6+/-0.8 ml/120 min) or not (0.5+/-0.3 ml/120 min). Losartan (50 microg/1 microl) partially reduced the effects of relaxin. The results show that central relaxin interacting with central angiotensinergic mechanisms induces NaCl intake after the blockade of LPBN serotonergic mechanisms.

Inhibition of sodium appetite by lipopolysaccharide: involvement of α2-adrenoceptors

Lipopolysaccharide (LPS), an endotoxin from the wall of Escherichia coli, produces a general behavioral inhibition and affects several aspects of fluid-electrolyte balance. LPS inhibits thirst; however, it is not clear if it also inhibits sodium appetite. The present results show that LPS (0.3-2.5 mg/kg body wt) injected intraperitoneally produces a dose-dependent reduction of sodium appetite expressed as 0.3 M NaCl intake induced by sodium depletion (furosemide plus removal of ambient sodium for 24 h). The high doses of LPS (1.2-2.5 mg/kg) also produced transient hypothermia at the beginning of the sodium appetite test; however, no dose produced hyperthermia. LPS also increased the stomach liquid content (an index of gastric emptying) after a load of 0.3 M NaCl given intragastrically by gavage to sodium-depleted rats. The α(2)-adrenoceptor antagonist yohimbine (5 mg/kg ip) abolished the effect of LPS on 0.3 M NaCl intake, without changing the effect of LPS on gastric emptying. Injection of RX-821002 (160 nmol), another α(2)-adrenoceptor antagonist, in the lateral cerebral ventricle (LV) also reversed the inhibition of sodium appetite produced by LPS. Yohimbine intraperitoneally or RX-821002 in the LV alone had no effect on sodium intake. Although yohimbine plus LPS produced a slight hypotension, RX-821002 plus LPS produced no change in arterial pressure, suggesting that the blockade of the effects of LPS on sodium intake by the α(2)-adrenoceptor antagonists is independent from changes in arterial pressure. The results suggest an inhibitory role for LPS in sodium appetite that is mediated by central α(2)-adrenoceptors.