Naloxone depresses osmoregulatory drinking in rats

The effect of an opiate antagonist, naloxone, on hypertonic NaCl-induced drinking was studied in rats in a within-subject design. Naloxone reduced drinking at all dosage levels used (0.3–10.0 mg/kg) when compared to a control condition. These results extend previous findings of naloxone mediated reduction in fluid intake in water deprived and osmotically challenged animals. Naloxone's effect on fluid intake seems to be independent of procedure employed, and thus quite general. Possible mechanisms were considered.     

Adipsic,but not anorectic,effect of fluprazine hydrochloride in rats

The present experiment explored the anorectic and adipsic effects of fluprazine hydrochloride, a phenylpiperazine compound. Thirty-eight albino rats were randomly assigned either to a control saline group (six rats) or to groups (eight subjects each) receiving an IP dose of fluprazine in saline (1.25, 2.5, 5 or 10 mg/kg). No anorectic effect of the drug doses was observed 30, 60, 90, 120, 180 and 240 min, and 24 h after drug injection. However, water drinking was significantly decreased 30 min after drug administration, with 5 and 10 mg/kg, compared to saline.     

Naloxone: Effects on food and water consumption in the non-deprived and deprived rat

Naloxone (0.5–5 mg/kg) reduced both food and water intake in non-deprived male rats, tested in the dark phase of the light-dark cycles in their home cages. These effects were transient; food and water-intake were restored to control levels by the end of the 8-h test period. The effects were also not dose-related. Naloxone (1 and 5 mg/kg) also reduced water-intake in water-deprived and food-deprived animals, without altering food-intake. These results suggested that naloxone may exert a primary antidipsogenic action, that does not depend upon any suppression of feeding. A final experiment showed that naloxone can completely abolish the thirst produced by injection of a hypertonic saline solution. This experiment also demonstrated that naloxone could suppress feeding, even though food intake was markedly inhibited by the osmotic thirst stimulus. Hence, the activation of feeding responses (e.g. by food deprivation) is not a necessary condition for naloxone to suppress feeding. The implications of these results for the control of feeding and drinking responses are briefly considered.     

Naloxone suppresses insulin-induced food intake in novel and familiar environments,but does not affect hypoglycemia

The opiate antagonist naloxone reduced the food intake induced in rats by acute injection of insulin. The suppression was most marked in the first hour after insulin injection. Insulin provoked less food intake when rats were tested in a novel environment compared with those tested in their home cage, but naloxone again significantly suppressed the intake in the first hour. Naloxone had no effect upon insulin-induced hypoglycemia.     

Suppression of deprivation-induced food and water intake in rats and mice by naloxone

Naloxone, an opiate antagonist, was administered to male and female rats and male mice after periods of food or water deprivation ranging from 12 to 48 hr. Naloxone (0.01-10 mg/kg) reduced postdeprivational water intake in most groups of rats and mice in a dose-related manner. Naloxone suppression of water consumption appeared to be independent of sexual differences in rats, and phase of the diurnal cycle, and length of the deprivation interval in both rats and mice. Postdeprivational food intake in male rats and mice was also reduced by naloxone in a dose-dependent fashion. This naloxone effect was less pronounced than actions observed with water intake, and tended to diminish with lengthening food deprivation periods. In general, mice appeared to be less sensitive than rats to naloxone suppression of food and water intake. Naloxone appears to markedly reduce appetitive behavior, particularly water intake, following deprivation in both rats and mice. The fact that low doses of naloxone can elicit these effects suggests that the drug is acting at specific tissue sites, possibly endorphine recpetors.     

Intraventricular glucose administration inhibits feeding in satiated but not in 24 hours food deprived cocks

Injection of 5 microliter isotonic glucose into the third ventricle above the basal hypothalamus but not in the posterior hypothalamus-anterior midbrain, suppressed feeding in satiated cocks. This suppression of food intake was less dramatic when glucose was injected after 5 hr of food deprivation and was eliminated if 24 hr of food deprivation preceded the glucose administration. An involvement of a glucostatic mechanism in the regulation of feeding in the chicken is suggested.     

Suppression of drinking by naloxone in rats homo- and heterozygous for diabetes insipidus

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 in adose-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.     

Naloxone-induced suppression of food intake in normal and hypothalamic obese rats

Intraperitoneal injections of naloxone hydrochloride (1, 2, 4, and 8 mg/kg) suppressed food intake in both normal and hypothalamic obese rats maintained on a 4-hr per day feeding schedule. The decrease in feeding was more pronounced in the animals with ventromedial hypothalamic lesions. Appetitively motivated feeding, i.e., the consumption of sweetened milk under nondeprived conditions, was also suppressed by naloxone, but there was no reliable difference between groups. It is concluded that opiate receptors located in the ventromedial hypothalamus are not essential for the effects of opiate agonists and antagonists on feeding behavior.     

Naloxone changes self-ratings but not performance in normal subjects

The effects of single intravenous doses of naloxone (0.8 and 1.6 mg) in a variety of performance tasks and on subjective ratings of mood and bodily symptoms were investigated in 12 student volunteers. Naloxone was without effect on any of the performance measures. However, 5 min after naloxone (1.6 mg) the subjects felt significantly more troubled, mentally slow, incompetent, withdrawn and physically tired, and less irritable. These effects appeared to be dose-related since 0.8 mg produced similar, but not statistically significant changes. Sixty-five minutes after the higher dose subjects felt significantly more muzzy and incompetent: in contrast to the effects at 5 min they now felt significantly more irritable. These results are difficult to explain solely in terms of opiate receptor blockade.Wellcome Trust Senior Lecturer     

The effect of ethanol on wheel running in rats

Rats were given IP injections of ethanol at 0, 400, 800 and 1200 mg/kg. Their activity in running wheels was recorded for one hour post-injection. Ethanol at 800 and 1200 mg/kg depressed running. This effect was greatest during the first 15 min post-injection when activity levels were highest in the nondrugged condition. No evidence of an ethanol-produced increase in running was seen. The monotonic, dose-related activity decrement with no biphasic effect from ethanol in wheel running is similar to some reports of this drug's effect on rats in other paradigms, such as food-motivated operant responding and spontaneous motor activity.     

Differential effects of morphine on food and water intake in food deprived and freely-feeding rats

In two experiments the effects of a range of doses of morphine (1, 3, 10 and 30 mg/kg) on the food and water consumption of rats were studied. The results of the first experiment showed that in 24 h food-deprived rats, morphine reduced levels of food and water intake. The duration of these actions was dependent upon dose, with only the highest dose (30 mg/kg) producing any effect persisting for longer than 4 h. In contrast a second experiment showed that morphine increased levels of food and water intake in non-deprived animals. The effect on food intake was most apparent when measurements were taken at 2 h and 4 h after drug administration, while water intake remained above control levels for over 6 h. This study shows that the actions of morphine on ingestion of food and water are affected by food deprivation, and the results are consistent with the hypothesised role of endogenous opiates in the mediation of such behaviour.     

The anorectic action of naloxone is attenuated by adaptation to a food-deprivation schedule

Recent studies have shown that naloxone and other opiate antagonists can reduce the amounts of food and water consumed by laboratory animals, a finding consistent with a role for endogenous opioids in the control of appetite. Because there have also been some failures to observe an anorectic action of naloxone, a study was carried out in which the effects of the drug on food intake were investigated using two different experimental procedures. In naive rats deprived of food for 24 h, both naloxone (0.1, 1.0 and 10.0 mg/kg) and fenfluramine (1.0, 3.0 and 10.0 mg/kg) produced dose-related decreases in food and water intake. In rats which has been adapted to receiving food for only 6 h each day, fenfluramine produced a similar effect whereas naloxone had no effect on food intake and reduced water consumption only at the highest dose. A second experiment showed that the different actions of a 1.0 mg/kg dose of naloxone in the two procedures were not due to differences in the duration of the immediately preceding period of food deprivation or in the time during which the rats were handled. These results show that the anorectic action of naloxone can be attenuated by adaptation to a schedule of repeated food deprivation.     

The effect of intracerebroventricularly infused satietin on conditioned taste aversion and feeding in rats fasted different lengths

Satietin is a glycoprotein (50,000-70,000 daltons MW) found in human serum (greater than 2 micrograms/ml) that is reported to be a strong anorexigenic agent when infused (10-100 micrograms/rat) intracerebroventricularly (ICV) into rats. The initial three experiments presented here explored whether satietin suppresses food intake by making the animals ill or causing them to experience malaise. A two-bottle taste aversion paradigm was used for this testing. In all experiments the rats were fitted with chronic third ventricle cannulas. After recovery from surgery the rats were trained for at least 6 days to drink their water in one hour a day, 1100-1200-hr (LD12:12-hr, lights out 12:00-hr). In Experiment 1 and 3 satietin (100 or 25 micrograms/rat) or vehicle was infused ICV 30 minutes prior to exposure to a novel neutral preference fluid flavor (banana or almond flavoring in water). Three days later the rats were given a choice of the two flavors to consume; this was repeated the next day. In both experiments satietin treated rats showed strong aversion to the flavor paired with satietin infusion, while saline infused controls showed no aversion. A similar paradigm was used during the second experiment, except satietin or vehicle infusion was paired with a highly preferred saccharin-water solution. Three days later the rats were given a choice between water and the saccharin-water solution. The satietin (50 micrograms/rat) treated rats exhibited a marked aversion to the saccharin-water solution. These data suggest that satietin may be an aversive substance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of opiates and naloxone on food intake in virgin and lactating rats

Lactation provides an excellent model of non-obese hyperphagia. There is accumulating evidence that endogenous opioids play a role in the modulation of the hormonal changes that occur during lactation. Because endogenous opioids appear also to play a role in the regulation of feeding, we studied the effects of the opiate agonist, butorphanol tartrate, and an opiate antagonist, naloxone, on food intake in virgin female rats and in rats during early, mid and late lactation and during post-weaning. It has been reported that female rats are less sensitive to the suppressant effects of nalmefene, an opioid antagonist, than male rats. Therefore, we also examined the effect of naloxone, an opioid antagonist, on spontaneous nocturnal feeding and 24 hour food deprivation-induced food intake in virgin female rats. We found that female rats were relatively insensitive to the food suppressant effects of naloxone following 24 hour food deprivation, while male rats tested under similar conditions had a decreased intake in response to naloxone. Despite the marked hyperphagia that occurred during lactation, there were minimal alterations in the response to opiate agonists and antagonists during this time period. Our data suggest that endogenous opioids may not play a pivotal role in the hyperphagia of lactation.     

Activation of 5-HT1C-receptors suppresses excessive wheel running induced by semi-starvation in the rat

Male Wistar rats were housed in cages linked to running wheels and fed on a schedule designed to reduce their body weight by 20–30%. During this period of semistarvation the rats increased their daily running wheel activity (RWA) by up to 30 km/day. RWA could be kept at this level provided that body weight was kept constant. Different serotonin receptor (5-HT) agonists and antagonists were tested for their effects on RWA and it was found that RWA could be suppressed only by agonists with high affinity for the 5-HT_1C receptor (TFMPP, mCPP, DOI and quipazine). Serotonin receptor agonists, which do not pass the blood-brain barrier, and 5-HT itself had no effect on RWA. The inhibitory effect of the agonists on RWA was prevented by pretreatment with antagonists that also had high affinity for 5-HT_1C receptors (mianserin, metergoline and mesulergine). From these results we conclude that semi-starvation-induced hyperactivity can be blocked by 5-HT_1C agonists. Furthermore we suggest that the animal model presented in this study might be a useful tool for in vivo studies on selective 5-HT_1C receptor activation.     

Naloxone and play fighting in juvenile rats

According to the opioid hypothesis of social attachment opiate receptor blockade should increase the need for social contact. Yet naloxone reduces play fighting [11], a major form of social interaction in young rats. This observation might be reconciled with the opioid attachment hypothesis if it could be shown that naloxone produced compensatory increases in other social activities or if naloxone shortened play fighting bouts without reducing their frequency. In the present experiment naloxone reduced play fighting in a dose-dependent fashion. However, the frequency of play bouts was reduced, their duration unchanged and no compensatory increase in social sniffing and grooming was observed. In addition, naloxone inhibited rearing almost as potently as it affected play fighting.     

Naloxone suppresses fluid consumption in tests of choice between sodium chloride solutions and water in male and female water-deprived rats

The effects of naloxone on fluid consumption by water-deprived rats trained to choose between a saline solution and water in a 15-min drinking test were examined. Rats of each sex were allocated to three groups and given access to 0.125% NaCl, 0.6% NaCl, and 1.7% NaCl, respectively, as the alternative to water. Under control conditions they drank substantially more of the hypotonic salt solutions than water, but drank slightly more water than hypertonic salt solution. Naloxone generally reduced fluid consumption, dose-dependently (0.01–10 mg/kg). In the cases of the two hypotonic solutions, the suppressant effect of naloxone was limited to saline solution. The usually low levels of water consumption were unaffected. In the case of the hypertonic solution, naloxone suppressed salt and water intakes by equivalent amounts. The effects of naloxone in the tests with the two higher salt concentrations depended upon sex. There was one example of a significant naloxone-induced reduction in saline preference (females; 0.125% NaCl v H₂O). In other instances, saline preferences were not significantly modified. The results are briefly discussed in relation to current suggestions that naloxone may affect fluid consumption in ways which are taste-dependent (e.g., taste sensitivity, palatability, reward). An alternative view is also considered, that the effects of naloxone may be taste-independent, at least in the particular case of drinking in a two-choice test with saline and water.     

Naloxone and fluid consumption in rats: dose-response relationships for 15 days

Rats were given daily intraperitoneal injections of 10.0, 1.0, 0.1, 0.01, 0.001 or 0.0 mg/kg naloxone for 15 days. Each day after the injections, animals were allowed access to a 20% sucrose solution for two hours and to tap water for the subsequent 10 hours. Consumption of the sucrose solution by the group that received 1.0 mg/kg was reliably decreased on Day 1 and 2, reflecting the suppressive effect of naloxone at that dose. By Day 3 until the end of the experiment, however, the suppression was no longer significant, suggesting that tolerance had developed. A similar effect was seen with the group given the highest dose, 10.0 mg/kg; although drinking was significantly less than the control in each of the 15 sessions, this group showed a trend to increase intake over the days of the experiment, thus also indicating possible tolerance to the effect of naloxone. Drinking patterns of the other groups did not differ statistically from the control. Thus, the low doses had no ability to suppress consumption, and the lowest dose that did lower it soon lost that ability; the highest dose continued to suppress drinking throughout the study but with decreasing efficacy. High performance liquid chromatography (HPLC) demonstrated that the naloxone remained intact over the 15 days of the experiment, supporting the suggestion that tolerance to naloxone might have developed.     

Effects of cyproterone acetate on growth and feeding in rats

Cyproterone acetate (CA) inhibited ponderal and linear growth and reduced food intake in juvenile male rats, but did not affect their water intake. CA reduced weight gain in young males that were unoperated, castrated, castrated and receiving testosterone propionate injections or adrenalectomized, but CA was not effective in inhibiting the already slow rate of growth in Males that were both adrenelectomized and castrated. CA similarly failed to affect body weight in juvenile or old females, but it did inhibit weight gain following ovariectomy. In old males that were no longer gaining weight CA reduced food intake and caused a loss of body weight. Although food intake was reduced by CA treatment, pair feeding studies indicated that other factors must also be involved in the reduced rate of weight gain. CA failed to affect pituitary or plasma GH levels and treatment with bovine GH did not alter the effects of CA on ponderal or linear growth or food intake.     

Naloxone, but not Tyr-MIF-1, reduces volitional ethanol drinking in rats: correlation with degree of spontaneous preference

The possible relationship between the actions of ethanol and opiates led us to examine the effect of opiate antagonists on ethanol intake in rats with a free choice of water. Naloxone (NAL) significantly reduced intake of ethanol. This effect was much greater in "high-preferring" (ethanol/total fluid intake greater than 60%) than in "low-preferring" (ethanol/total fluid intake less than 30%) rats. Furthermore, a correlation was found between the degree of spontaneous preference (ethanol/total fluid intake ratio) and the reduction of ethanol drinking by NAL. Sensitivity to NAL increased with increased preference for ethanol. Neither Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) nor MIF-1 (Pro-Leu-Gly-NH2) caused a significant modification of ethanol intake. This study shows that NAL can reduce volitional ethanol intake in rats and provides further evidence that Tyr-MIF-1 does not always act like NAL.