naloxone and Diabetes-Insipidus

The analgesic effect of electrical stimulation of the hypothalamic paraventricular nucleus (PVN) was studied. Additionally, the involvement of vasopressin and opioid peptides in this process was examined by comparing vasopressin-deficient (Brattleboro) and Long-Evans rats and by administering the opiate antagonist naloxone. Rats were chronically implanted with a stimulating electrode in the parvocellular (PVN-Pc) and magnocellular (PVN-Mg) divisions of the PVN. At least 10 days after surgery, the analgesic effects of PVN stimulation were examined in lightly anesthetized rats, using the tail-flick method, and in unanesthetized rats, using the hot-plate test. PVN stimulation produced marked analgesia in both tests. Current threshold for analgesia was lower from PVN-Pc than from PVN-Mg. Threshold did not differ significantly between Brattleboro and Long-Evans rats and was not affected by naloxone administration. The results indicate that the PVN is part of the brain's pain inhibitory system, and show that the analgesia induced by PVN stimulation is not mediated by either vasopressin or opioid peptides.

Topics: Analgesia; Animals; Brain Stem; Diabetes Insipidus; Dynorphins; Electric Stimulation; Electrodes, Implanted; Endorphins; Male; Naloxone; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reaction Time; Spinal Cord; Vasopressins

1. Subcutaneous injection of the kappa-opioid agonists U50,488 (10 mg kg-1) and tifluadom (3.5 mg kg-1) into Inactin-anaesthetized, saline-infused rats was associated with a diuresis, antinatriuresis and antikaliuresis which lasted for up to 2 h. A high (5 mg kg-1), but not low (0.1 mg kg-1), dose of naloxone blocked the renal effects of U50,488. 2. U50,488 administration in anaesthetized, vasopressin-deficient Brattleboro DI rats was associated with an attenuated diuresis, though the antinatriuretic response remained intact. 3. The diuretic action of U50,488 was associated with an increase in glomerular filtration rate while fractional fluid reabsorption remained steady. In contrast, fractional sodium and potassium reabsorption were increased. 4. These data suggest that kappa-opioid agonists alter renal handling of both water and electrolytes. This appears to be mediated by two separate mechanisms: increased fluid loss largely reflects altered glomerular events while the fall in electrolyte excretion results from altered tubular handling.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Anesthesia; Animals; Arginine Vasopressin; Diabetes Insipidus; Electrolytes; Glomerular Filtration Rate; Male; Naloxone; Potassium; Pyrrolidines; Rats; Rats, Brattleboro; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Sodium

The development of an acute hemorrhagic shock in rats with hereditary diabetes insipidus (DI), lacking vasopressin, is very dramatic, compared to rats of the parent strain Long Evans (LE). After removal of 50% of the circulating blood for LE, and 30% for DI, the mortality for both LE and DI groups was 50%, the shock index being 0.049 and 0.028, respectively. Infusion of either vasopressin (107 mU/100 g) or naloxone (0.2 mg/100 g) in DI rats, prevented the progression of hemorrhagic shock into irreversible stage, and augmented survival up to 66% and 57%, respectively. The specific opioid antagonist naloxone exerted a therapeutic effect on rats with hemorrhagic shock by antagonism of opioid receptors, without influencing ACTH and aldosterone secretion in DI rats. This is another evidence for the role of beta-endorphin in the pathogenesis of hemorrhagic shock.

Topics: Acid-Base Equilibrium; Adrenocorticotropic Hormone; Aldosterone; Animals; Blood Pressure; Diabetes Insipidus; Heart Rate; Male; Naloxone; Rats; Rats, Brattleboro; Receptors, Opioid; Renin; Respiration; Shock, Hemorrhagic; Vasopressins

The effect of naloxone (0.6 mg; 1.2 mg; 2.4 mg X kg-1) were compared in normal Long Evans (N) and Brattleboro (D.I.) conscious rats. Naloxone did not change the values of drinking, diuresis, food intake, blood pressure, Na+ and K+ urinary excretion measured during 24 hours. During the two hours following drug injection, naloxone (1.2 and 2.4 mg X kg-1) reduced diuresis in normal as well as in D.I. rats. Water drinking was only modified in D.I. rats: this effect was shown to be a consequence of antidiuresis. These results suggest that the antidiuretic properties of naloxone are independent of vasopressin secretion. They do not support in a role of opiate receptors on vasopressin secretion in normal hydrated animals.

Topics: Animals; Body Water; Diabetes Insipidus; Diuresis; Drinking; Eating; Naloxone; Rats; Rats, Inbred Strains; Vasopressins

Brattleboro rats placed in metabolism cages were injected with morphine (Mor), naloxone (Nal), D- and L-aspartic acid (D- and L-Asp), D-phenylalanine (D-Phe), D-leucine (D-Leu) and prolyl-leucyl-glycinamide (PLG), alone and in suitable combinations. Food and fluid intake, urine outflow, faeces weight, rectal temperature and urinary osmolality were determined at the end of seven hours period of time. Mor, Nal, D-Asp and PLG alone caused a significant decrease in food and fluid intake, urine volume and faeces weight and a significant increase in urinary osmolality being the osmolality of the Mor, D-Asp and PLG injected groups higher than 300 mOsmol/kg. The combination of Nal with Mor, D-Asp and PLG appeared to intensify the changes induced by Mor, D-Asp and PLG whereas L-Asp antagonized the majority of changes caused by Mor or PLG. The results were discussed in the light of the previous experimental findings.

Topics: Amino Acids; Animals; Body Temperature; Diabetes Insipidus; Drinking Behavior; Feces; Feeding Behavior; Female; Morphine; Naloxone; Oligopeptides; Osmolar Concentration; Rats; Rats, Brattleboro; Stereoisomerism; Urine

The effects of naloxone (2 and 10 mg kg-1 s.c.) were compared in several kinds of experimental polyuria: alcohol- or water-loaded rats and Brattleboro rats (i.e. animals with congenital lack of vasopressin). In normal rats, both water and alcohol increased urine flow and decreased urinary osmolality. Alcohol induced a more marked diuretic response than water. In normally hydrated rats, naloxone (2 and 10 mg kg-1 s.c.) failed to modify urine flow, urinary osmolality, Na+ and K+ urinary excretion, and urine creatinine concentration. The two doses of naloxone decreased urine flow and increased osmolality in both water- and alcohol-loaded rats. In Brattleboro rats, naloxone (10 mg kg-1 s.c.) reduced urine flow and urinary creatine whereas the low dose (2 mg kg-1 s.c.) was without effect. Since it is well known that the mechanism of water- or alcohol-induced diuresis is an inhibition of vasopressin release, the present results suggest that naloxone could prevent this inhibition. They indicate that endogenous opioid peptides may exert an inhibitory control on vasopressin release.

Topics: Animals; Creatinine; Diabetes Insipidus; Diuresis; Ethanol; Male; Naloxone; Natriuresis; Potassium; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins; Water

The effects of the opiate antagonist, naloxone, alone and in combination with morphine, were examined on drinking induced by water deprivation in homo- and heterozygous Brattleboro rats manifesting an inherited diabetes insipidus. Both naloxone and a structurally-related congener, naltrexone (0.01-10 mg/kg), attenuated water consumption is a dose-related fashion of 1 hr water-deprived homozygotes, which exhibit a complete absence of vasopressin. Drinking was also reduced by the two drugs in 24 hr water-deprived heterozygotes, which have detectable levels of vasopressin. Morphine pretreatment enhanced the antidipsogenic effects of naloxone in a dose- and time-dependent manner. The administration of 10 mg/kg of morphine 3 hr before testing, which itself did not affect drinking, maximally potentiated the suppressant effects of naloxone on drinking in homozygotes. This potentiating effect of morphine persisted for at least 48 hr. These results indicate that vasopressin is not essential for the antidipsogenic effects of the narcotic antagonists. The polydipsic Brattleboro rat may provide a convenient animal model for studies of the effects of opiate agonists and antagonists on drinking behavior.

Topics: Animals; Diabetes Insipidus; Drinking Behavior; Heterozygote; Homozygote; Male; Morphine; Naloxone; Naltrexone; Rats; Rats, Inbred Strains; Time Factors

1 beta-Endorphin (2 micrograms injected into the lateral ventricles) produced a significant decrease in the urine outflow and in the excretion of Na+ and K+ in Brattleboro rats, animals suffering from severe diabetes insipidus. Morphine intracerebrally also produced antidiuresis, as compared to saline-treated controls. 2 Morphine injected intraperitoneally caused a dose-dependent decrease in the urine outflow, and in the excretion of Na+ and K+. 3. Rats chronically treated with morphine (72 h of morphine pellet implantation) were less sensitive to the antidiuretic effect of a challenge dose of morphine than control Brattleboro rats implanted with placebo pellets, but otherwise treated similarly. 4 After chronic morphine administration, Brattleboro rats became dependent on morphine. Challenge with 1 mg/kg naloxone (s.c.) precipitated an abrupt opiate withdrawal syndrome characterized, among other symptoms, by increased urination in contrast to the antidiuresis observed before naloxone.

Topics: Animals; beta-Endorphin; Diabetes Insipidus; Diuresis; Drug Tolerance; Endorphins; Female; Humans; Morphine; Morphine Dependence; Naloxone; Natriuresis; Potassium; Rats

Topics: Animals; Diabetes Insipidus; Diuresis; Dogs; Male; Morphine; Naloxone; Receptors, Opioid; Vasopressins