Decreased Water Intake Research Articles

Thermal dehydration-induced thirst in rats: role of angiotensin II

Dehydration can be brought about by either water deprivation or by heat exposure (thermal dehydration). Angiotensin II has been shown to have a role in water deprivation-induced thirst. The current study was designed to determine whether angiotensin II is involved in thirst caused by thermal dehydration. Male Sprague-Dawley strain rats were dehydrated by exposure to a 40 degree C environment for 2-4 h or by water deprivation for 44 h. Water deprivation but not heat exposure significantly increased plasma renin activity. Neither ureteric ligation nor nephrectomy significantly altered water intake after thermal dehydration. Captopril, an inhibitor of angiotensin converting enzyme, given at a dose of 100 mg/kg ip, significantly decreased water intake in water-deprived rats but not in thermally dehydrated rats. Angiotensin II therefore does not appear to play a role in the control of water intake of thermally dehydrated rats. The physiological responses to dehydration in rats are dependent on the way in which the dehydration is brought about.

Intra-midbrain raphe injections of the neurokinin-3 agonist senktide inhibit food and water intake in the rat

Microinjection and lesion studies have implicated the midbrain dorsal (DR) and median raphe (MR) nuclei in behavioral arousal. This behavioral state is manifested as locomotor hyperactivity, hyperphagia, hyperdipsia and increases in plasma corticosteroid release. Intra-midbrain raphe injections of the GABA A agonist muscimol elicit this behavioral activation. We have demonstrated that similar infusions of tachykinins produce locomotor hyperactivity through activation of neurokinin-3 (NK-3) receptors located on serotonin cell bodies. The purpose of the present study was to determine the effects of intra-MR and DR infusions of senktide, an NK-3 agonist, on food and water consumption in nondeprived rats. Male Sprague-Dawley rats were implanted with indwelling intra-MR or intra-DR cannula. Infusions of muscimol (25 ng/0.5 μl) into the MR increased water intake, while MR and DR infusions increased food consumption. In contrast, intra-MR injections of senktide decreased water intake and intra-MR and DR injections decreased food intake. The results suggest that the behavioral states induced by muscimol and neurokinin infusions into the raphe are distinct and that raphe/neurokinin pathways are involved in consummatory mechanisms.

Rat brain natriuretic peptide (BNP) reduces water intake following dehydration

The effect of rat brain natriuretic peptide (BNP) on drinking behaviour was examined in dehydrated and well-hydrated rats. Following dehydration for 18h, intracerebroventricular injections of 5 μg of rat BNP significantly reduced water consumption 0–2 h after the injections, but not 2–4 h afterwards. Rat BNP failed to decrease water intake in animals given water ad libitum. Thus, rat BNP is similar to alpha-atrial natriuretic polypeptide in that it only affects drinking in dehydrated rats. Following dehydration, plasma vasopressin levels were decreased by BNP, but BNP did not affect serum osmolality and electrolyte metabolism. These findings suggest that BNP may be involved in the central regulation of water consumption.

Is the behavioural effect of diazepam in rats unique to negative secondary stimuli?

Studies of the behavioural effects of benzodiazepines have focused in particular on situations with negative secondary stimuli, i.e., stimuli signalling negative primary events such as punishment or non-reward. The general result is that benzodiazepines attenuate behavioural reactions to this type of stimuli. The aim of the present study was to investigate if there are any differences between positive and negative secondary stimuli in this respect. Rats were treated with diazepam in a modified Skinner box with two levers. One of the levers always gave a small reward. A lamp being ON or OFF was used as a secondary stimulus indicating if the other lever would give a large or no reward. Pretreatment with diazepam (1.0 mg/kg) did not act differently on the response to the positive or negative secondary stimulus. The main effect was a general attenuation of optimal responding with a concomitant decrease in water intake. An alternative hypothesis stating that benzodiazepines alter the reactivity to secondary stimuli more in general is supported.

Effects of a selective mu opioid receptor agonist and naloxone on the intake of sodium chloride solutions

Endogenous opioid peptides are thought to play a role in mediating the palatability or rewarding aspects of sweet tastes. There is also evidence, however, which suggests that opioids may influence the preference for the taste of salt as well. In the present studies, we measured the effects of central administration of naloxone and the mu agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on the ingestion of salt solutions. In non-deprived rats given a choice of water and 0.6% saline, ICV injections of DAGO (1 and 3 nmol) significantly increased the intake of 0.6% saline; baseline water intake was minimal and was unaffected by DAGO. When rats were given a choice between water and 1.7% saline, DAGO stimulated both water and saline intake. Because 1.7% saline is a hypertonic solution, the increase in water intake may have been secondary to saline intake. In rats on a deprivation schedule in which water and 0.6% saline were available for only 2-3 h/day, there was a tendency for DAGO to increase 0.6% saline intake and decrease water intake, though these effects were not significant. In rats given water and 1.7% saline, DAGO increased saline intake and had no effect on water intake. Naloxone was also tested in water-deprived rats. Naloxone (20 and 50 micrograms) significantly decreased 0.6% saline intake; baseline water intake was low (3-5 ml) and was unaffected by naloxone. When rats were given a choice between water and 1.7% saline, naloxone (50 micrograms) significantly reduced water intake, while intake of 1.7% saline was slightly increased. These results suggest a role for central mu opioid receptors in mediating the preference for salt solutions.

Differential attenuation of water intake and water-rewarded operant responding by repeated administration of haloperidol and SCH 23390 in the rat

It has previously been described that water intake in thirsty rats require higher doses of dopamine (DA) D-1 and D-2 antagonists to be attenuated than operant lever-pressing with water as reward. In the present study, effects of repeated administration of the DA D-1 antagonist SCH 23390 and the DA D-2 antagonist haloperidol were investigated in the same experimental paradigm. In agreement with previous reports, attenuation of operant responding increased progressively by haloperidol (0.05 mg/kg) given for four consecutive days. However, this attenuation was not accompanied by decreased water intake, tested for in parallel experiments. After haloperidol (0.2 mg/kg), in contrast, a progressively decreasing attenuation of water intake was found. After SCH 23390, both the initial attenuation of lever-pressing (0.02 mg/kg) and consummatory water intake (0.1 mg/kg) became less pronounced over time. The results thus show that: 1) the previously reported progressively increasing attenuation of operant responding caused by repeated administration of D-2 antagonists is not mimicked by the D-1 antagonist SCH 23390, and 2) attenuation of water intake caused by higher doses of neuroleptics is, in direct opposition, less pronounced after repeated administrations. The results also show that attenuation of operant responding by neuroleptics cannot solely be dependent upon a blunting of the impact of the reward.

Comparison of the toxicity of inorganic and liver-incorporated cadmium: A 4-wk feeding study in rats

The toxicity of cadmium was examined in rats fed diets containing either tissue-incorporated cadmium or cadmium salt for 4 wk. The test diets contained 30 mg cadmium/kg either as cadmium chloride, or as cadmium incorporated in pigs' livers; the control group was fed a diet containing liver from a pig not treated with cadmium. Over 90% of the cadmium present in the pigs' livers was bound to metallothionein. Analysis of the diet and determination of the food consumption revealed that both cadmium-fed groups were exposed to similar dietary cadmium levels. There was no adverse effect on general health or survival. Feeding cadmium resulted in growth retardation and slightly decreased water intake. Moreover, both cadmium-treated groups showed clear signs of anaemia and increased plasma aspartate and alanine aminotransferase activities. For the group fed cadmium chloride, all of these effects were more pronounced than for the group fed cadmium incorporated in liver. Microscopic examination of the liver and kidneys, however, did not reveal any lesion that could be attributed to the cadmium treatment. After exposure to cadmium the spleen showed decreased extramedullary haematopoiesis, an effect that was also more pronounced after feeding of the cadmium chloride than after feeding liver-incorporated cadmium. The differences in the extent of the toxic effects between the inorganic and the tissue-incorporated cadmium were accompanied by differences in the cadmium concentrations in liver and kidneys: the feeding of cadmium incorporated in pigs' livers resulted in about half the accumulation of cadmium in the rats' livers that took place after intake of a diet containing cadmium chloride. In contrast a much less marked difference in cadmium accumulation was observed in the kidneys. Since humans are usually exposed to tissue-incorporated cadmium these findings deserve further investigation, with special attention to the observed difference in tissue accumulation.

Effects of sigma agonist and antagonist drugs on food and/or water intake in rats

AbstractDrugs known to interact with sigma receptors were studied for their effects on food and/or water intake, since the putative sigma receptor agonist N‐allylnormetazocine (NANM) has been reported to both increase and decrease food intake under various conditions. Previous investigators have shown that each enantiomer of racemic NANM [(±)‐NANM] is pharmacologically active. (+)‐NANM appears to interact preferentially with sigma receptors, and (−)‐NANM with both mu and kappa opiate receptor sites. In the present study, the effects of subcutaneously administered (±)‐NANM, (+)‐NANM, and (−)‐NANM on food intake in 20 hr food‐deprived male rats were examined. (±)‐NANM and (−)‐NANM decreased food intake stimulated by food deprivation, while (+)‐NANM exhibited no significant effect. Similarly, both (±)‐NANM and (−)‐NANM decreased water intake in 24 hr water‐deprived rats. (+)‐NANM decreased water intake in doses which may have caused disorientation. Locomotor activity was stimulated by intraperitoneal injection of 10 mg/kg of (+)‐NANM but not by the same dose of (−)‐NANM. The effects of (+)‐NANM and (−)‐NANM on food and water intake paralleled those of narcotic antagonists and did not seem related to an interaction with sigma receptors. (±)‐BMY14802 is a sigma receptor antagonist with potential antipsychotic properties. When administered to female rats by daily injection for 28 days, it did not affect weight gain except at the highest dose, 30 mg/kg. Weight gain of animals given a 30 mg/kg dose was significantly greater compared to controls. However, rats treated orally with a similar dose of (±)‐BMY14802 incorporated into the diet daily for 8 weeks did not exhibit significant weight gain compared to controls. The data argue against a significant role for sigma receptors in mediating ingestive behavior. Should sigma antagonist drugs reach the market, they may be less likely to cause weight gain than most classical antipsychotics.

Toxicology studies of a chemical mixture of 25 groundwater contaminants: II. Immunosuppression in B6C3F 1 mice

Concern over the potential adverse health effects of chemically contaminated groundwater has existed for many years. In general, these studies have focused on retrospective epidemiological studies for cancer risk. In the present studies, immune function was monitored in female B6C3F 1 mice exposed to a chemical mixture in drinking water for either 14 or 90 days. The mixture consisted of 25 common groudwater contaminants frequently found near toxic waste dumps, as determined by EPA surveys. None of the animals developed overt signs of toxicity such as body or liver weight changes. Mice exposed to the highest dose of this mixture for 14 or 90 days showed immune function changes which could be related to rapidly proliferating cells, including suppression of hematopoietic stem cells and of antigen-induced antibody-forming cells. Some of these responses, e.g., granulocyte-macrophage colony formation, were also suppressed at lower concentrations of the chemical mixture. There were no effects on T cell function or T and B cell numbers in any of the treatment groups. Altered resistance to challenge with an infectious agent also occurred in mice given the highest concentration, which correlated with the immune function changes. Paired-water studies indicated that the immune effects were related to chemical exposure and not to decreased water intake. These results suggest that longterm exposure to contaminated groudwater may represent a risk to the immune system in humans.

Effects of repeated administration of low doses of apomorphine in three behavioural models in the rat

A low dose of the dopamine (DA) receptor agonist apomorphine (APO 0.05 mg/kg) was given repetitively and the effects were tested in three different behavioural models: reduction of spontaneous locomotion, induction of yawning and decrease in water intake in water-deprived animals. The APO-induced suppression of exploration and decrease in water intake were not affected by a previous injection of APO given 1 or 3 hours before the test dose of APO. There was a small, but significant, decrease in the induction of yawning by a previous dose of APO given 1 hour or 30 min before the test dose. However, pretreatment with APO 3 hours before the test dose did not diminish the yawning response. It is suggested that the dopaminergic mechanisms mediating APO induced yawning are different from those mediating decrease in water intake and suppression of exploration. The results are also discussed in relation to the proposed efficiency of low doses of DA agonists in the treatment of various neurological and psychiatric disorders.

Attenuation of water intake and operant responding by dopamine D2 antagonists: raclopride provides important cues for understanding the functional mechanism of action.

The selective dopamine (DA) D2 receptor antagonist raclopride was found to attenuate operant lever-pressing with water as reward in a dose dependent manner and more potently than the corresponding consummatory act, i.e. the unconditioned water intake. This is the same way as previously reported for other DA D2 antagonists. In screening experiments raclopride has been selected on the basis of great separation between antagonism of DA-agonist induced hyperactivity, stereotypies and production of catalepsy. We found that attenuation of lever-pressing and water intake by raclopride were not more separated in dose than after, for example, haloperidol. We further found that attenuation of lever-pressing and water intake occurred in doses relatively lower than those producing catalepsy, thus excluding catalepsy as a cause for the attenuation. Decreased water intake in thirsty animals caused by a low dose of apomorphine (APO) was counteracted by raclopride. This has previously been found with DA D2, but not with D1, antagonists, which further supports that this apomorphine-effect is mediated via D2 receptors. However, raclopride only showed this antagonism in a narrow dose-range, like haloperidol. The selective profile previously found for sulpiride, proposed to be related to low incidence of extrapyramidal side-effects in the clinic, was thus not replicated.

Effects of the dopamine D-1 antagonist SCH 23390 on water intake, water-rewarded operant responding and apomorphine-induced decrease of water intake in rats

The specific dopamine (DA) D-1 receptor antagonist SCH 23390 was found to attenuate operant lever-pressing with water as reward in a dose-dependent manner and more potently than drinking itself. This effect occurred in the same fashion as previously reported for DA D-2 antagonists. In contrast to the DA D-2 antagonist haloperidol, the attenuated operant lever-pressing induced by the DA D-1 antagonist SCH 23390 was not counteracted by the anticholinergic drug scopolamine. The decreased water intake in thirsty animals caused by a low dose of apomorphine was not antagonised by SCH 23390. This has previously been found with DA D-2 antagonists, such as haloperidol and sulpiride. The results show that in spite of some similarities in the behavioural effects of DA D-1 and D-2 antagonists, a closer pharmacological analysis is able to reveal pronounced differences.

Effects of acute and chronic anti-panic drug administration on conflict behavior in the rat

The present studies were undertaken to evaluate further the utility of the Conditioned Suppression of Drinking (CSD) conflict paradigm as an animal model for the study of panic disorder and anti-panic agents. In daily 10-min sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA). Electrification was signalled by a tone. Desipramine (DMI), amitriptyline (AMI), or phenelzine (PHEN) was administered both in acute (10-min pre-treatment) and chronic (twice daily for up to 9 weeks) regimens. Acute administration of DMI, AMI or PHEN over a wide range of doses resulted in no change or a decrease in the number of shocks accepted and a decrease in water intake at higher doses. In contrast, chronic administration of each agent resulted in a gradual (2-4 week latency) increase in the number of shocks received in CSD sessions over the course of several weeks of testing. This time-dependent increase in punished responding in the CSD observed during chronic anti-panic drug treatment parallels the time-dependent reduction in the severity and frequency of panic attacks in panic disorder patients receiving chronic antidepressants. Thus, the CSD paradigm might serve as an animal model for the study of panic disorder and potential anti-panic agents.

Dopamine D-2 antagonists reverse apomorphine-induced decreased water intake in the rat: prediction of antipsychotic drugs with few extrapyramidal side-effects?

Water intake in water deprived rats was decreased by administration of a low dose of apomorphine (0.1 mg/kg s.c.). This dose is too low to induce hyperactivity and stereotypies. Four different dopamine (DA) D-2 antagonists were used to counteract this effect of apomorphine; haloperidol [an antipsychotic inducing extrapyramidal side-effects (EPS)], sulpiride (an antipsychotic inducing less EPS than haloperidol), metoclopramide (not used as an antipsychotic but inducing EPS) and domperidone (not passing through the blood brain barrier). Domperidone did not counteract the apomorphine effect, indicating a central mechanism of action for apomorphine. Metoclopramide did not counteract the apomorphine effect and, in higher doses, water intake was even further reduced. Sulpiride completely counteracted the apomorphine effect but, in higher doses, did not by itself reduce water intake. Haloperidol counteracted the apomorphine effect in a small dose-range and caused a further reduction in the water intake when given in high doses. The results can be explained by the existence of two subpopulations of D-2 receptors related to different functions. The model described may be used in screening experiments aimed at finding new antipsychotic drugs with a low incidence of EPS.

MR/Har and MNRA/Har Maudsley rat strains: Differential response to chlordiazepoxide in a conflict task

The Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rat strains, selectively bred for differences in open field defecation, have also been shown to differ in their baseline behavior in the Conditioned Suppression of Drinking (CSD) procedure, a second “model” behavior for the study of anxiety and/or emotionality in rats. The present studies were designed to compare the responsiveness of these two strains to the typical antianxiety agent chlordiazepoxide in the CSD paradigm. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube that was occasionally electrified (0.5 mA), electrification being signaled by a tone. Consistent with previous reports, after several weeks of CSD testing, MNRA/Har rats accepted significantly more shocks than did MR/Har rats during control (nondrug) sessions. In both strains, the number of shocks accepted was inversely related to the intensity of the shock used (0.25–1.0 mA), with MNRA/Har rats accepting significantly more shocks than MR/Har rats at all intensities examined. The effects of various doses (1.25–28.4 mg/kg, IP) of chlordiazepoxide were determined in subjects of the MNRA/Har strain at the original training intensity (0.5 mA), while a lower intensity (0.25 mA) was utilized in MR/Har rats. Although punished responding in control (i.e., nondrug) CSD sessions did not differ under these conditions, MNRA/Har rats were found to be more responsive to the anticonflict effects of chlordiazepoxide than rats of the MR/Har strain. This strain difference in anticonflict efficacy of chlordiazepoxide was quite dramatic, with MNRA/Har rats accepting twice as many shocks as MR/Har rats following maximally effective doses of chlordiazepoxide. Low doses of chlordiazepoxide increased water intake slightly, while higher doses decreased water intake. Surprisingly, the chlordiazepoxide-induced depression of water intake was greater in rats of the MR/Har strain. Thus, these Maudsley Reactive and Non-Reactive rat strains, bred originally for their differences in open field behavior, also differ markedly in their responsiveness to chlordiazepoxide in the CSD paradigm. These findings further support the hypothesis that the MR/Har and MNRA/Har rat strains may represent a genetically-based “animal-model” for the study of emotionality and/or anxiety.

Inhibition of drinking by naltrexone in the rat: Interaction with the dopamine D-1 antagonist SCH 23390 and the D-2 antagonist sulpiride

The involvement of dopamine receptors in water intake was investigated in the rat deprived of water for 24 hr. A 0.03 mg/kg dose of SCH 23390 markedly enhanced naltrexone (0.1 and 10.0 mg/kg)-induced hypodipsia, whilst the drug alone significantly decreased water intake at doses of 0.01 to 3.0 mg/kg, accompanied by marked motor dysfunction. Sulpiride (20.0 and 40.0 mg/kg) did not markedly affect water intake and naltrexone-induced hypodipsia. Consistent with previous results, apomorphine (0.3 mg/kg) alone was without marked effects, while it produced a marked potentiation of naltrexone (1.0 and 10.0 mg/kg)-induced hypodipsia. SCH 23390 (0.003 mg/kg) and sulpiride (40.0 mg/kg) completely antagonized the enhancing effects of apomorphine on naltrexone-induced hypodipsia. Similar effects were also seen in the latency to begin drinking. In contrast to the effects on naltrexone-induced hypodipsia, it appears that both dopamine D-1 and D-2 receptors play a key role in the effects of apomorphine on naltrexone-induced hypodipsia in the rat.

A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforced behavior

Lever-pressing responses of 55 rats were reinforced with IV-delivered cocaine (0.2 mg/kg) or saline under conditions of continuous access for 15 24-h sessions. The rats also responded on tongue-operated drinking devices for deliveries of a 3% (w/v) glucose + 0.125% (w/v) saccharin (G+S) solution or water. The effects of removing these substances on behavior maintained by G+S, water, cocaine, or saline were compared in 11 groups. Terminating cocaine access produced a decrease in G+S drinking and an increase in food and water intake. In contrast, a group of rats that did not initially self-administer G+S showed increases in G+S drinking when cocaine was removed, and G+S-maintained responding persisted when cocaine was reinstated. Substitution of water for G+S produced a nearly two-fold increase in cocaine-reinforced behavior but no change in IV-delivered saline self-administration in a control group. A group that did not initially self-administer cocaine increased its infusion rate to over 400 infusions per day as soon as G+S was replaced with water. The effect of presenting cocaine to a group that responded for G+S alone was to decrease G+S intake, but there was only a transient decrease in water intake in the control group. Likewise, presentation of G+S to a group of rats self-administering cocaine resulted in a decrease in infusions, but saline infusions did not change in a control group. Generally, there was an increase in food and water intake during cocaine removal, but food and water intake did not vary systematically with the removal or presentation of G+S.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of Effect of Dietary Factors on Nicarbazin Toxicity in Broiler Chicks

Effects of dietary fat, protein, and methionine levels and the type of dietary grain in nicarbazin-containing diets on the growth response of broiler chicks were evaluated in five experiments in a factorial design. Nicarbazin at levels ranging from 100 to 200 mg/kg significantly (P<.05) depressed weight gain and feed efficiency. Feed intake was significantly reduced only when nicarbazin was used at levels of 150 and 200 mg/kg. The latter concentration also significantly decreased water intake and water:feed ratio. Nicarbazin, at a level of 150 mg/kg, did not affect dietary metabolizable energy content or the retention of nitrogen and dry matter.A higher level of soybean oil (3.5 vs. .5 or 1.0%) did not counteract the growth-depressing effects of 100, 150, and 200 mg nicarbazin/kg. The growth-depressing effect of the highest dose also was not affected by increasing the protein level from 18.2 to 20.4%. Neither type of dietary grains (corn vs. sorghum) nor supplemental methionine level affected the toxicity of 125 mg nicarbazin/kg. Water intake and water:feed ratio were significantly increased due to elevation of dietary protein and fat levels. It was concluded that the severity of the growth-depressing effect of nicarbazin on chicks was not dependent on the levels of dietary unsaturated fat, protein, and methionine.

Modification of immunological responses and clinical disease during topical R-837 treatment of genital HSV-2 infection

R-837, a compound with no in vitro anti-HSV activity, was administered intravaginally to guinea pigs (5 mg/kg every 12 h) for five days beginning 12 h after genital HSV-2 inoculation. Drug treatment reduced vaginal viral replication ( P<0.0001), completely protected against primary disease and reduced recurrent genital HSV disease ( P<0.0001). Drug treatment also induced mild fever, weight loss, and decreased water intake. R-837 was a potent interferon inducer, which also induced variable enhancement of cell-mediated cytolytic activity against HSV-2 targets. Less than 36 h of vaginal HSV shedding was observed in animals with R-837 induced early enhancement of HSV-target cytolysis. Compared to placebo, R-837 decreased ELISA and ADCC antibody to HSV-2, but accelerated HSV-2 specific in vitro IL-2 production and peripheral blood mononuclear cell (PBMC) proliferation. R-837 exhibited potent anti-HSV activity in vivo apparently due to cytokine induction and enhancement of cell-mediated responses.

Effects of intrahypothalamic administration of opioid peptides selective for μ-, κ-, and δ-receptors on different schedules of water intake in the rat

The effects of opioid peptides selective for μ-, κ-, and δ-opioid receptors were investigated on 3 different schedules of water intake in the rat: spontaneous, deprivational (12 h), and hypertonic saline-induced drinking. Peptides were injected into the paraventricular and supraoptic hypothalamic nuclei. d-Ala- 2-NMePhe 4-Gly(ol)-enkephalin, a μ-selective opioid agonist, tended to increase water intake in non-deprived rats, but 0.01 and 0.1 μg significantly decreased water intake for 45 min in deprived rats, and for up to 60 min in hypertonic saline-injected rats when injected into the paraventricular hypothalamic nucleus. The κ-selective agonist, dynorphin A 1–13 (0.1, 0.3, 1.0 and 3.0 μg) and the δ-selective agonist, [ d-Pen 2, l-Pen 5]enkephalin (0.3 and 3.0 μg) did not affect spontaneous, deprivation or hypertonic saline-induced water intakes when injected into either the paraventricular or supraoptic hypothalamic nuclei. Thus, a μ-selective opioid peptide produced dose- and time-dependent effects on drinking that were pharmacologically and anatomically specific, and dependent upon the schedule of water intake.