Zinc and water intake in rats: investigation of adrenergic and opiatergic central mechanisms

We have demonstrated that central administration of zinc in minute amounts induces a significant antidipsogenic action in dehydrated rats as well as in rats under central cholinergic and angiotensinergic stimulation. Here we show that acute third ventricle injections of zinc also block water intake induced by central ß-adrenergic stimulation in Wistar rats (190-250 g). Central inhibition of opioid pathways by naloxone reverses the zinc-induced antidipsogenic effect in dehydrated rats. After 120 min, rats receiving third ventricle injections of isoproterenol (160 nmol/rat) exhibited a significant increase in water intake (5.78 ± 0.54 ml/100 g body weight) compared to saline-treated controls (0.15 ± 0.07 ml/100 g body weight). Pretreatment with zinc (3.0, 30.0 and 300.0 pmol/rat, 45 min before isoproterenol injection) blocked water intake in a dose-dependent way. At the highest dose employed a complete blockade was demonstrable (0.54 ± 0.2 ml/100 g body weight). After 120 min, control (NaAc-treated) dehydrated rats, as expected, exhibited a high water intake (7.36 ± 0.39 ml/100 g body weight). Central administration of zinc blocked this response (2.5 ± 0.77 ml/100 g body weight). Naloxone pretreatment (82.5 nmol/rat, 30 min before zinc administration) reverted the water intake to the high levels observed in zinc-free dehydrated animals (7.04 ± 0.56 ml/100 g body weight). These data indicate that zinc is able to block water intake induced by central ß-adrenergic stimulation and that zinc-induced blockade of water intake in dehydrated rats may be, at least in part, due to stimulation of central opioid peptides

Central lead administration inhibits water intake and sodium appetite in rats

We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5 percent). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite

Opiatergic participation in the thirst-inhibiting effect of acute third ventricle injections of cadmium (Cd 2+ ) and lead (Pb 2+ )

We have previously demonstrated that acute third ventricle injections of both lead and cadmium prevent the dipsogenic response elicited by dehydration or by central injections of dipsogenic agents such as angiotensin II, carbachol and isoproterenol in rats. We have also shown that the antidipsogenic action of cadmium may be due, at least in part, to activation of thirst-inhibitory central serotonergic pathways. In the present paper we show that in Wistar male rats the antidipsogenic effect of both lead acetate (3.0 nmol/rat) and cadmium chloride (3.0 nmol/rat) may be partially dependent on the activation of brain opiatergic pathways since central injections of naloxone (82.5 nmol/rat), a non-selective opioid antagonist, blunt the thirst-inhibiting effect of these metals. One hundred and twenty minutes after the second third ventricle injections, dehydrated animals (14 h overnight) receiving saline + sodium acetate displayed a high water intake (7.90 ñ 0.47 ml/100 g body weight) whereas animals receiving saline + lead acetate drank 3.24 ñ 0.47 ml/100 g body weight. Animals receiving naloxone + lead acetate drank 6.94 ñ 0.60 ml/100 g body weight. Animals receiving saline + saline drank 8.16 ñ 0.66 ml/100 g body weight whilst animals receiving saline + cadmium chloride drank 1.63 ñ 0.37 ml/100 g body weight. Animals receiving naloxone + cadmium chloride drank 8.01 ñ 0.94 ml/100 g body weight. It is suggested that acute third ventricle injections of both lead and cadmium exert their antidipsogenic effect by activating thirst-inhibiting opioid pathways in the brain

Lead (Pb+) and cadmium (Cd2+) inhibit the dipsogenic action of central beta-adrenergic stimulation by isoproterenol

We have previously demonstrated that acute third ventricle injections of both Pb2+ and Cd2+ impair the dipsogenic response elicited by three different situations: dehydration and central cholinergic or angiotensinergic stimulation. beta-Adrenergic activation is part of the multifactorial integrated systems operating in drinking behavior control in the central nervous system. In the present study acute third ventricle injections of Pb2+ (3,30 and 300 pmol/rat) or Cd2+ (0.3, 3 and 30 pmol/rat) blocked the dipsogenic response induced by third ventricle injections of isoproterenol (ISO; 160 nmol/rat) in a dose-dependent manner. Normohydrated animals receiving ISO + NaAc (sodium acetate) or saline (controls) displayed a high water intake after 120 min (ISO + saline = 5.78 ñ O.54 ml/lOO g; ISO + NaAc = 6.00 ñ O.6 ml/lOO g). After the same period,animals receiving ISO but pretreated with PbAc at the highest dose employed (300 pmol/rat) drank O.78 ñ O.23 ml/lOO g while those receiving ISO and pretreated with the highest dose of CdCl(2)(30 pmol/rat) presented a water intake of O.7 ñ O.30 ml/lOO g. Third ventricle injections of CdCl(2) (3 nmol/rat) or PbAc (3 nmol/rat) did not modify food intake in rats deprived of food for 24 h. Thus, general central nervous system depression explaining the antidipsogenic action of the metals can be safely excluded. It is concluded that both Pb2+ and Cd2+ inhibit water intake induced by central beta-adrenergic stimulation.

Calcium channel blockers inhibit the antidipsogenic effect of central injections of zinc in rats

Previous data from our laboratory have indicated that acute third ventricle injections of Zn2+ elicit a significant antidipsogenic response in rats in three different situations: dehydration, and central angiotensinergic or cholinergic stimulation. In the present study we analyzed whether this response depends on voltage-dependent calcium channels. Dehydrated (l4 h of water deprivation, overnight) animals received 2-mul icv injections of zinc acetate (Zn(AC)2; 300 pmol/rat) after pretreatment with the voltage-dependent calcium channel blockers gadolinium (Gd3+;0.03, 3.0 and 30 pmol/rat) or verapamil (VER; 0.027, 0.05 and 0.11 pmol/rat). Both blockers reversed the antidipsogenic effect of third ventricle injections of Zn2+ in a dose-dependent manner. After 120 min, animals pretreated with saline receiving Zn(AC)2 drank 3.10 ñ 0.57 ml/100 g body weight while those pretreated with GD3+ at the highest dose displayed a water intake of 5.45 ñ O.41 ml/l00 g body weight (P<0.01). Animals pretreated with the vehicle of VER receiving Zn(AC)2 drank 3.15 ñ 0.45 ml/l00 g while animals pretreated with VER at the highest dose receiving Zn(AC)2 drank 6.16 ñ 0.62 ml/l00 g (P<0.01). The antidipsogenic effect of Zn(AC)2 seems to be specific since the metal (same dose and injection procedures) did not modify food intake in rats after 24 h of food deprivation. It is suggested that Zn2+ exerts its antidipsogenic effect by activation of mechanism(s) depending on the functional integrity of voltage-dependent calcium channels.

SDZ 216-525, a selective 5-Ht1A receptor antagonist, reverts zinc-induced inhibition of water intake in dehydrate rats

Zinc is found in many brain regions where it participates in important processes such as neurotransmission and neuromodulation. We previously demonstrated that acute third ventricle injection of zinc inhibits wather intake in dehydrated rats. The present study was undertaken to explore a possible link between zinc-induced inhibition of water intake in dehidrated rats and seotonergic systems in the brain. Adult, male Wistar rats had the third ventricle cannulated a week before the experiments. After an overnight period of water deprivation, the animals (N=12 per group) received acute intracerebroventricular injections (2µl) of Zn(Ac)2 (6.7, 67.1 and 67.6 ng/rat). Control animals (N = 12) receives NaAc (671.6 ng/rat). Zinc-treated animals displayed a significant after 120 min was 7.70 ñ 0.50 ml in control (NaAc-treated) dehydrated rats while animals treated with the highest dose of Zn(AC)2 drank 2.63 ñ 0.73 ml. Third ventricle injections of SDZ 216-525, a selective 5-HT1A receptor antagonist, 45 min before zinc administration, generated a dose-dependent reversal of zinc-induced thirst blockade in water-deprived rats. At the highest dose used (10µg/rat), the water intake of the animal after 120 min was 7.30 ñ 0.23 ml, a value equal to that of control animals. These data suggest that zinc may decrease water intake in dehydrated rats by activation of a 5-HT1A receptor-related mechanism