The role of putative 5-HT1A and 5-HT1B receptors in the control of feeding in rats.

8-hydroxy-2(di-n-propylamino)tetraline (8-OH-DPAT) and 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)1H indole succinate (RU 24969), two agonists on the putative serotonin 1A and serotonin 1B receptors, were used for exploring the role of these sites in the inhibitory effect of serotonin (5-HT) on feeding. In free-feeding rats, 2.5-5 mg/kg RU 24969 significantly reduced food intake while doses of 8-OH-DPAT ranging from 0.125 to 0.5 mg/kg increased eating. The effects of the highest doses were associated with hyperlocomotion and hyperreactivity for RU 24969 and a typical motor syndrome (flat body posture and forepaw treading) for 8-OH-DPAT. The motor syndrome caused by 0.5 mg/kg 8-OH-DPAT was much more obvious in food-deprived rats in which food intake was also markedly reduced. RU 24969 1.25 and 5 mg/kg reduced food intake by food-deprived rats and caused hyperlocomotion not different from that in free-feeding animals. Pretreatment with metergoline (2 mg/kg i.p.) prevented the effect of 5 mg/kg RU 24969 on food intake by food-deprived rats but had no effect on the reduction of eating caused by 0.5 mg/kg 8-OH-DPAT. The motor syndrome caused by 8-OH-DPAT was not changed by metergoline but the hyperlocomotion caused by RU 24969 was potentiated. Haloperidol (0.1 mg/kg i.p.) completely blocked the hyperlocomotion but did not change the reduction of food intake caused by RU 24969 in food-deprived rats. It is suggested that the putative serotonin 1B receptors specifically mediate the inhibitory effect of 5-HT on feeding whereas serotonin 1A sites act by enhancing eating only in free-feeding animals.

Patterns of ethanol and water consumption as a function of restricted ethanol access and feeding condition.

Sixteen male albino rats were divided into two groups of eight animals and maintained at either their free-feeding or at 80% of their free-feeding weight. For four animals, access to 8% ethanol was unrestricted, for the remaining four, access was restricted to eight 20-min access periods per day. Mean amounts of ethanol consumed per bout were greater during restricted access than during unrestricted access for food-deprived animals but not for free-feeding animals. Total daily ethanol consumption was greatest when animals were food deprived and access to ethanol unrestricted. Total fluid consumption and the within session distribution of water and ethanol responding were affected by feeding condition. For food-deprived animals, the amount of water consumed per session remained relatively constant. The increase in ethanol consumption over sessions resulted in an increase in total fluid consumption. For the free-feeding animals, increases in ethanol consumption resulted in decreases in water consumption so that total fluid consumption remained constant. In addition, food-deprived animals consumed all their daily water intake at the beginning of each session when food was present. Free-feeding animals consumed water throughout the session.

Drug and environmentally induced manipulations of the opiate and serotonergic systems alter nociception in neonatal rat pups.

The influence of drug- and environmentally induced alterations in serotonergic and opiate activity on pain sensitivity was assessed in 6-day-old Sprague-Dawley-derived rat pups using tail flick-testing procedures. The opiate agonist morphine was observed to induce tail flick analgesia that was blocked by concurrent administration of the opiate antagonist naloxone. Similarly, the serotonergic agonist quipazine induced analgesia that was blocked by pretreatment with the serotonergic antagonist metergoline. Naloxone alone did not alter tail flick responsivity in non-isolated, nondeprived neonates, suggesting that the opiate system may not exert a significant tonic inhibition of pain sensitivity in neonates. In contrast, the serotonergic system may exert some tonic analgesic influence at this age, given that metergoline was observed to induce slight hyperalgesia in nondeprived, non-isolated neonates. Twenty four hours of food and maternal deprivation, shown previously to increase brain serotonin and 5-hydroxyindole acetic acid and their ratio in neonates (L. P. Spear & F. M. Scalzo, 1984, Developmental Brain Research, in press) was observed to induce tail flick analgesia, an effect blocked by metergoline. Isolation from siblings and the dam and nest for 30 min also induced tail flick analgesia; this analgesia was blocked by treatment with naloxone prior to testing. Together, these experiments support the suggestion that the serotonergic and opiate systems may regulate pain sensitivity even in neonatal rat pups, with agonist- or environmentally precipitated increases in serotonergic or opiate activity inducing significant analgesia during the early postnatal period.

Cyclophosphamide and inhibition of renal compensatory hypertrophy.

The objective of the present study was to determine whether cyclophosphamide inhibits nephrectomy-induced compensatory renal hypertrophy directly or indirectly owing to the reduced food intake caused by the drug. We measured kidney weight and renal water, protein, deoxyribonucleic acid (DNA), and ribonucleic acid (RNA) content and the renal RNA/DNA ratio in 72 rats distributed into groups as follows: left nephrectomized/cyclophosphamide-treated rats; left nephrectomized/saline treated rats; left nephrectomized rats submitted to food restriction and treated with saline; and left sham-nephrectomized rats treated with saline. An additional group of 12 rats was studied to obtain the initial values of the parameters. The parameters were also measured 1, 2 and 3 weeks after left nephrectomy or sham-operation. Cyclophosphamide was given once a week intraperitoneally at the dosage of 60 mg/kg body weight in saline. Corresponding volumes of saline were given to control animals. At the end of the 1st week all nephrectomized groups of rats showed some degree of renal compensatory growth. However, no significant differences in kidney weight, protein or RNA content were detected between controls, cyclophosphamide-treated rats, and animals submitted to food restriction at the end of the 2nd and 3rd week. We conclude that cyclophosphamide inhibits but does not abolish compensatory renal hypertrophy after uninephrectomy in the young rat and this inhibition is mediated primarily through the reduced food intake caused by the drug.

Insulin effect on in vivo gluconeogenesis from [3-14C]pyruvate in the starved rat.

During a 24 hr fast rats received 4 subcutaneous injections of insulin, and 15 min after the last injection they were given an intravenous pulse of [3-14C]pyruvate. The amount of [14C]glucose in blood 2 min after the tracer did not differ between insulin treated and control animals, whereas at 5 and 10 min values were significantly lower in the former group. At 10 min after the tracer, liver [14C]glycogen specific activity and [14C]fatty acid amount were higher in the insulin treated animals than in controls while plasma concentration of gluconeogenic amino acids was lower in the first group. Similar changes but less pronounced and more retarded were found in 24 hr fasted rats given only one insulin dose 15 min before the [3-14C]pyruvate pulse. Results indicate that gluconeogenesis from pyruvate is not directly modified by insulin treatment. Effects found at 5 and/or 10 min after the tracer and reported effects after prolonged insulin treatments may be caused by one or all of the following possibilities: enhanced utilization of the new-formed glucose, reduced availability of gluconeogenic substrates, and counteracting action on gluconeogenic hormones.

Self-administration of orally-delivered methohexital in rhesus monkeys with phencyclidine or pentobarbital histories: effects of food deprivation and satiation.

Orally-delivered methohexital was demonstrated to function as a reinforcer for rhesus monkeys with either phencyclidine or pentobarbital self-administration histories. The effects of food deprivation and food satiation were compared across a wide range of methohexital concentrations. Initially, three monkeys were trained to orally self-administer phencyclidine (0.25 mg/ml) and water, and three were trained to orally self-administer pentobarbital (0.5 mg/ml) and water under concurrent fixed-ratio (FR) schedules during daily 3-hr sessions. Liquid deliveries during the session (drug and water) and intersession (water) were contingent upon lip contact responses on solenoid-operated drinking spouts. The monkeys were first tested while food deprived by maintaining them at 85% of their free-feeding body weights. Methohexital concentrations were presented in the following order, and each concentration was held constant until at least five or six sessions of stable behavior were obtained: 2, 2.8, 4, 2 (retest), 1, 0.5, (plus 0.25 and 0.125 in monkey M-W) and 2 (retest) mg/ml. The monkeys were then food satiated by allowing them unlimited access to food, and the methohexital concentration series was repeated. During food deprivation, the concentration-response functions generally resembled an inverted U. Concurrent water-maintained responding was generally low, but it increased in some monkeys as methohexital concentrations increased in some monkeys. During food satiation, methohexital-maintained responding was not different from water-maintained responding in some monkeys, but in others it was substantially higher than water-maintained responding. Maximum drug intake ranged from 20.4 to 93.8 mg/kg during food deprivation and from 6.4 to 64.2 during food satiation among the six monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chlordiazepoxide on food anticipation, drinking and other behaviors in food-deprived and satiated rats.

Two groups of rats, Deprived and Satiated, were presented with food according to a fixed time 60-sec schedule. They were then injected with saline, 5, 10, and 15 mg/kg of chlordiazepoxide hydrochloride according to a Latin square design. During saline administration time spent visiting the food tray, time spent drinking, number of tray entries and the amount of water ingested were always greater in the Deprived than in the Satiated group; whereas the opposite was true for grooming. As chlordiazepoxide dose increased time spent visiting the food tray increased in both groups, but the effect was bigger in the Satiated than in the Deprived group. Drinking was not affected by the drug. Grooming and sniffing-rearing were reduced as the dose increased.

Changes in marrow myelopoietic and lymphoid cell counts after repeated cyclophosphamide administration in the rat.

Rat marrow myeloid and lymphoid counts were estimated after repeated doses of cyclophosphamide injected intraperitoneally. It was found that in order to evaluate the bone marrow response, a quantitative approach is a necessity. Myelotoxic and lymphotoxic effects in the bone marrow following repeated doses of cyclophosphamide were markedly similar to suppression which followed the restriction of food consumption. Relationships between rat white blood and marrow counts were analyzed. Convenience of determination of marrow cellularity for measurement of myelotoxic effects is discussed with respect to studies with repeated administration of cytostatic agents.

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 hr. 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 hr and after 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.