Effect of the intracerebroventricular administration of GR 113808, a selective 5-HT4 antagonist, on water intake during hyperosmolarity and hypovolemia

We demonstrate here that acute third ventricle injections of GR 113808, a highly selective 5-HT4 antagonist, decrease water intake induced by a previous salt load while potentiating drinking elicited by hypovolemia induced by previous subcutaneous administration of polyethylene glycol in male Wistar rats (200 + or - 20 g). At the dose of 160 nmol/rat, third ventricle injections of GR 113808 induced a significant reduction of water intake in salt-loaded animals after 120 min as compared to salt-loaded animals receiving third ventricle injections of saline (salt load + GR = 3.44 + or - 0.41 ml, N = 12; salt load + saline = 5.74 + or - 0.40 ml, N = 9). At the dose of 80 nmol/rat, GR 113808 significantly enhanced water intake in hypovolemic animals after 120 min as compared to hypovolemic animals receiving third ventricle injections of saline (hypovol + GR = 4.01 + or - 0.27 ml, N = 8; hypovol + saline = 2.41 + or - 0.23 ml, N = 12). We suggest that central 5-HT4 receptors may exert a positive drive on water intake due to hyperosmolarity and a negative input on drinking provoked by hypovolemia.

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

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.

Effects of central epinephrine synthesis inhibition on stress-induced prolactin secretion in male rats

1. The present study was designed to examine the role of central epinephrine pathways in the control of stress-induced prolactin secretion in male adulto Wistar rats. 2. Intracerebroventricular adminsitration of two epinephrine synthesis inhibitors, SKF64139 (5 and 10 µg/rat) and LY 134046 (10 and 20 µg/rat), 6 h before the onset of immobilization stress blocked prolactin secretion in a dose-dependent manner. Prolactin values before stress were about 4.0 ng/ml and increased to almost 50 ng/ml in the control group. SKF 64139 injection in the higher dose (10 µg/rat) induced a complete blockade of the stress-induced prolactin release, whereas partial blockade was observed after the higher dose (20 µg/rat) of LY 134046. 3.Salbutamol pretreatment (10 µg/rat) completely restored stress-induced prolactin secretion in animals receiving a central injection of both epinephrine synthesis inhibitors under the same conditions as described above. 4. It is suggested that epinephrine pathways in the brain play an important role in the control of prolactin release occuring during immobilization stress