Central serotonergic and adrenergic/imidazoline inhibitory mechanisms on sodium and water intake

Recent studies have shown the existence of two important inhibitory mechanisms for the control of NACL and water intake: one mechanism involves serotonin in the lateral parabrachial nucleus (LPBN) and the other depends on alpha(2)-adrenergic/imidazoline receptors probably in the forebrain areas. In the present study we investigated if alpha(2)-adrenergic/imidazoline and serotonergic inhibitory mechanisms interact to control NaCl and water intake. Male Holtzman rats with cannulas implanted simultaneously into the lateral ventricle (LV) and bilaterally into the LPBN were used. The ingestion of 0.3 M NaCl and water was induced by treatment with the diuretic furosemide (10 mg/kg of body weight)+the angiotensin converting enzyme inhibitor captopril (5 mg/kg) injected subcutaneously 1 h before the access of rats to water and 0.3 M NaCl. Intracerebroventricular (i.c.v.) injection of the alpha(2)-adrenergic/imidazoline agonist clonidine (20 nmol/1 microl) almost abolished water (1.6+/-1.2, vs. vehicle: 7.5+/-2.2 ml/2 h) and 0.3 M NaCl intake (0.5+/-0.3, vs. vehicle: 2.2+/-0.8 ml/2 h). Similar effects were produced by bilateral injections of the 5HT(2a/2c) serotonergic agonist 2,5-dimetoxy-4-iodoamphetamine (DOI, 5 microg/0.2 microl each site) into the LPBN on water (3.6+/-0.9 ml/2 h) and 0.3 M NaCl intake (0.4+/-0.2 ml/2 h). Injection of the alpha(2)-adrenergic/imidazoline antagonist idazoxan (320 nmol) i.c.v. completely blocked the effects of clonidine on water (8.4+/-1.5 ml/2 h) and NaCl intake (4.0+/-1.2 ml/2 h), but did not change the effects of LPBN injections of DOI on water (4.2+/-1.0 ml/2 h) and NaCl intake (0.7+/-0.2 ml/2 h). Bilateral injections of methysergide (4 microg/0.2 microl each site) into the LPBN increased 0.3 M NaCl intake (6.4+/-1.9 ml/2 h), not water intake. The inhibitory effect of i.c.v. clonidine on water and 0.3 M NaCl was still present after injections of methysergide into the LPBN (1.5+/-0.8 and 1.7+/-1.4 ml/2 h, respectively). The results show that the inhibitory effects of the activation of alpha(2)-adrenergic/imidazoline receptors in the forebrain are still present after blockade of the LPBN serotonergic mechanisms and vice versa for the activation of serotonergic mechanisms of the LPBN. Therefore, each system may act independently to inhibit NaCl and water intake.