Peripheral administration of urocortin suppresses operant responding for food reward.

The effects of peripheral systemic administration of urocortin on operant responding to obtain food were investigated using three separate concentrations. The drug was administered intraparitoneally at a concentration of 10 microg/ml/Kg, 5 microg/ml/Kg, and 0 microg/ml/Kg suspended in saline at a volume of 1 ml/Kg to Sprague-Dawley rats fifteen minutes prior to being exposed to an operant bar press task. Eleven subjects were used, each receiving a single injection of each concentration on separate days with the order of treatment counterbalanced. The results indicated that the administration of urocortin in a dose dependent manner reduced responding of food deprived subjects for a food reward in a thirty minute session. These data indicated that the peripheral administration of urocortin reduced the motivation of food deprived subjects to respond.

Subchronic cocaine produces training paradigm-dependent learning deficits in laboratory rats.

The effect of cocaine on spatial learning was investigated by exposing male Sprague-Dawley rats to 0, 20, or 40 mg/kg cocaine prior to and during training on a water maze task. Half the animals were pretrained on cued trials prior to hidden platform trials, while the remaining animals completed hidden platform trials immediately. Escape latencies for all animals improved with training, but pretrained animals located the hidden platform faster than untrained animals (P<.001). Pretraining also decreased the effect of cocaine. In pretrained animals, only the high dose of cocaine caused significant increases in escape latency (P<.001), while in the untrained group the lower dose of cocaine also caused a significant increase (P<.001). On working memory measures, cocaine affected both the pretrained (P<.01) and untrained (P<.001) groups. Dwell ratio measurements indicated unaffected reference memory in both pretrained (P<.001) and untrained (P<.001) animals, and no significant differences were detected among the treatment conditions in either group (P>.05). Thus, while cocaine did not abolish learning, the efficiency with which the task was learned was compromised. However, this effect was reduced by pretraining.

Food deprivation does not influence body or selection temperature in rats receiving intraventricular bombesin.

Bombesin (BBS), a tetradecapeptide, has been found to have potent hypothermic effects when centrally administered. This study was designed to investigate the relationship between food-deprivation and BBS-induced hypothermia in a temperature selection paradigm. Food-deprived and satiated male Sprague-Dawley rats were given intracerebroventricular (ICV) injections of several doses of BBS and control vehicle. Selection temperature data and changes in core body temperature were measured. BBS produced a significant hypothermia and decrease in selection temperatures in all doses but one. No significant differences in body temperature or selection temperatures were found between food-deprived and satiated animals. The results are consistent with the hypothesis that BBS acts centrally to decrease body temperature set point.

Effects of cocaine on dietary self-selection during pregnancy and lactation in the rat.

Previously, we have shown that patterns of food selection are altered by pregnancy and lactation in rats. Reproductive animals increase total food intake during gestation and lactation, and select more carbohydrate and protein during lactation than virginal controls. In other self-selection studies, female rats administered cocaine compensate for decreases in carbohydrate and fat but not protein intake, resulting in a potential protein deficiency. The present study was designed to test the combined effects of cocaine and reproductive period on food intake. Cocaine was administered daily (PO) to 18-h food-deprived rats during the second and third week of gestation and the first week of lactation. Immediately following drug administration, each animal had free access to isocaloric carbohydrate, protein, and fat in a dietary self-selection situation. Intake of each component was measured at 30 min, 60 min, 2 h, and 6 h following the drug treatment. The results of this study indicate that cocaine administration during gestation and lactation disrupts normal patterns of food intake. Altered patterns of food intake may be responsible for some of the deleterious effects of maternal cocaine use on offspring.

The effects of cocaine on dietary self-selection in female rats.

Cocaine was administered via an oral route to 18-h food deprived female rats for 14 consecutive days. Following administration of the drug or vehicle control each animal was presented with separate isocaloric rations of protein, fat, and carbohydrate in a dietary self-selection situation. Amounts consumed of each component were measured at 30 min, 60 min, 2 h, and 6 h following the drug treatment. The intake of all three macronutrients was suppressed by cocaine for 1 h. Between 2 and 6 h after administration, there was a compensatory increase in fat and carbohydrate, but not protein consumption. The results are discussed in terms of protein deficiency caused by cocaine in pregnant and/or lactating females being a causal factor in the deleterious effects on offspring.

Capsaicin does not attenuate bombesin-induced suppression of operant responding for food reward.

Systemic treatment with capsaicin, a neurotoxin which damages unmyelinated peptide-containing sensory neurons, has been shown to attenuate bombesin (BBS)-induced suppression of food intake. To determine whether capsaicin-sensitive fibers mediate the effect of BBS on appetitive motivation, we examined BBS-induced suppression of operant responding in rats pretreated neonatally with capsaicin (50 mg/kg; SC) or control vehicle. At 8-10 weeks of age, rats were trained to bar press for food. After achieving a stable level of performance, the animals were injected with BBS (10 micrograms/kg), normal saline, or prefed with 20 Noyes 45-mg pellets. Animals were then tested in an operant chamber on an FR 5 schedule of reinforcement for one hour. The results indicated that BBS suppressed bar pressing, regardless of whether animals were pretreated with capsaicin or control vehicle. These findings are inconsistent with the hypothesis that BBS induces satiety via capsaicin-sensitive neurons. The results suggest the possibility that more than one mechanism may mediate the effects of BBS: a neural mechanism involved in consummatory responses and a humoral mechanism involved in the operant response.

The effects of pregnancy and lactation on dietary self-selection in the rat.

Total food intake and intake of discrete dietary components, carbohydrate, fats, and protein, throughout pregnancy and lactation were measured in the albino rat, with virginal rats acting as controls. The dietary components were isocaloric and presented in a self-selection situation. Although the reproductive subjects ate more carbohydrate, protein, and total food than controls during the lactation phase, their intake did not significantly exceed that of controls during pregnancy. In addition, reproductive but not virginal animals changed patterns of selection over the reproductive periods. They consumed more total food during gestation and lactation, and more carbohydrate and protein during lactation.

An inexpensive gradient for temperature selection in rodents.

The construction of a horizontal temperature gradient is described in detail. The apparatus is built from readily available and inexpensive materials. The chamber is built from PVC tubing, fitted with an aluminum floor, and placed in a sound-attenuated box. A temperature gradient is formed by placing solid CO2 at one end and a hot plate at the opposite end of an aluminum floor. The apparatus described is reliable, dependable, and has proven to be very suitable for use with small rodents.

The effects of intraventricular injections of bombesin on temperature selection in the rat.

The purpose of these experiments was to elucidate further the possibility that intraventricular injections of bombesin (BBS) lower the set point around which an animal regulates its core body temperature. In an attempt to prevent a confounding of general activity and thermoregulatory behavior which occurred in earlier work, a horizontal temperature gradient was used. Intraventricular injections of bombesin resulted in the selection of temperatures that were approximately 9-13 degrees C colder than those selected by animals following control injections. Additionally, the increase in core body temperature observed following control injections was reversed by the highest dose of bombesin. No significant alterations in general locomotor activity were observed. These findings suggest that bombesin may act centrally to reduce the set point around which behavioral responses are regulated.

Bombesin: potential integrative peptide for feeding and satiety.

The neuropeptide bombesin (BBS) is examined with regard to possible designation as an integrative peptide. The term integrative peptide has been proposed to distinguish a subset of regulatory peptides. These peptides, distributed in the body and the brain, may function as hormones and neurotransmitters to integrate physiological and psychological functions. It is suggested that BBS may function as a peripheral and central satiety-inducing agent. The specific topics with regard to BBS include: feeding, satiety, and aversion; peripheral and central effects; learning, memory, and reward; route of injection; taste modulation; gastrointestinal activity; neurotransmitter status; mechanism and neuroanatomical site of action; and neural and humoral transmission.

Intake of individual macronutrients following IP injections of BBS and CCK in rats.

The effects of injections of either bombesin (BBS) or cholecystokinin octapeptide (CCK-8) on patterns of food intake of macronutrients were examined in adult male rats, and compared to the effects following saline injections. The animals were food deprived for 18 hours and then offered one of three isocaloric dietary components (protein, carbohydrate or fat). During the first 30 minutes following injections of BBS, protein intake was decreased. Suppression of carbohydrate intake, significant between 30 and 60 minutes, was sustained up to two hours following injections. During the first 30 minutes following injections of CCK, animals reduced their intake of each macronutrient. Reductions in the consumption of fat and protein were sustained up to one and six hours, respectively. The availability of particular macronutrients is proposed as a possible factor accounting for differences among studies with respect to self-selection profiles and duration effects.

Bombesin improves rats' operant responding maintained by a differential-reinforcement-of-low-rates schedule of food reinforcement.

The present study examined rats' responding on a differential-reinforcement-of-low-rates schedule of food reinforcement following intraperitoneal injections of various doses of bombesin (4, 6, 8, 16, 32 micrograms/kg). Analyses indicated that only the 6 micrograms/kg dosage improved DRL responding. The findings are consistent with prior research examining bombesin's effect on operant behavior and support the notion that bombesin induces satiety rather than malaise.

Peripheral injections of bombesin and cholecystokinin affect dietary self-selection in rats.

Patterns of dietary self-selection were examined in adult female rats following peripheral injections of either bombesin (BBS) (6, 10, 14 and 16 micrograms) or cholecystokinin octapeptide (CCK-8) (0.75, 1.5, 2.25, and 3.0 micrograms). Animals were food deprived for 18 hours and then offered three isocaloric diets (protein, carbohydrate, and fat) following injections of peptides. Each subject received each of 4 doses of both peptides in a within-subjects design. All doses of BBS decreased total food intake and fat intake 30 minutes following injections. Also at this time period the two highest doses suppressed carbohydrate intake, while protein was unaffected. Cumulative intake at one hour revealed that total intake remained suppressed. The two highest doses continued to suppress carbohydrate intake, while only the 14 micrograms dose continued to suppress fat intake. Additionally protein was now significantly suppressed by all doses. The three highest doses of CCK-8 produced a decrease in total food intake and fat intake 30 minutes after injections. By one hour, only total intake remained suppressed but only with administration of the highest dose. Results are interpreted as providing support for the notion that BBS and CCK are physiological satiety signals and that they maintain unique functions in regulating food intake.

Cholecystokinin and bombesin suppress operant responding for food reward.

The effects of intraperitoneal injections of cholecystokinin (CCK) and bombesin (BBS) on food-rewarded operant responding were investigated. Response rates were significantly suppressed following administrations of CCK (0.7, 1.4, and 2.9 micrograms/kg). The effects appeared to be dose dependent. Responding was also suppressed following injections of BBS (6 and 16 micrograms/kg). These results confirm and extend previous findings concerning the possible function of these peptides.

Suppression of operant responding for food and water reinforcement following intraventricular injections of Bombesin in the rat.

The effects of injecting Bombesin (BBS) into the lateral cerebral ventricle on operant responding for food and water in the rat were investigated in two experiments. In the first experiment injections of BBS suppressed both operant responding for water and post-session water consumption. A combined treatment of water preloading and BBS injections produced greater suppression of post-session water consumption than either BBS injections or water preloading. This suggests that the peptide has a primary antidipsic effect. In the second experiment BBS produced a significant suppression of operant responding for food reward as well as lowered body temperature. This suggests that BBS may serve as a true satiety signal for food motivated behavior.

Injections of bombesin into the substantia nigra produce hypothermia and hypophagia in food-deprived rats.

Hypothermia and hypophagia have been elicited, under a variety of experimental conditions, by central injections of bombesin. The preoptic area of the anterior hypothalamus has been suggested as the active site for the hypothermia observed in rats exposed to cold, while the lateral hypothalamus has been implicated in the production of hypophagia induced by bombesin. Data are reported here demonstrating a significant, dose-related decrease in both intake of food and body temperature following microinjections of bombesin into the substantia nigra of male rats deprived of food for 18 hr. Similar injections into the preoptic area, the lateral hypothalamus and the ventromedial hypothalamus failed to produce a consistent decrease in either intake of food or body temperature. Although a decrease in body temperature was demonstrated following injections into the paraventricular nucleus of the hypothalamus, this decrease did not appear to be dose-related. Injections of bombesin at this site had no effect on food intake. The possibility of an underlying dopaminergic mechanism for the hypothermic and hypophagic effects of bombesin is discussed.

Effects of centrally-administered bombesin and adrenalectomy on behavioral thermoregulation and locomotor activity.

Bombesin is an oligopeptide which has been implicated as a possible neurotransmitter or neuromodulator in the central nervous system. Central administration of the peptide produces physiological and behavioral responses which suggest a downward shift in the set point of body temperature. These include hypothermia, decreased metabolic rate and increased behavioral responding to escape from radiant heat. Contradictory data also exist. Therefore, a series of experiments was conducted to evaluate further the effects of the central administration of bombesin on behavioral thermoregulation and general locomotor activity. It was found that microinjections of bombesin into the preoptic area of the anterior hypothalamus increased the number of behavioral responses to radiant heat. The increased responding for heat-reinforcement and heat-escape suggested an activation of general locomotor activity. This was confirmed by the finding that centrally-administered bombesin increased the number of responses to escape from radiant heat without altering the duration of exposure to heat. Additionally, bombesin had no effect on the number of heat-escape responses following adrenalectomy. It was concluded that bombesin acts within the hypothalamus to increase general locomotor activity via the sympathetic outflow to the adrenals. This behavioral excitation is apparently expressed as an increase in responding to heat, or escape from heat, independent of thermoregulatory mechanisms. Therefore, the behavioral data do not indicate that bombesin decreases the set point of body temperature.

The effects of injections of bombesin into the cerebral ventricles on food intake and body temperature in food-deprived rats.

Central injections of bombesin have been shown to produce hypothermia in animals exposed to a cold environment, but not in animals maintained under thermoneutral conditions. Peripheral injections have been associated with decreased food intake in rats. The data reported here demonstrate a significant, dose-related decrease in both body temperature and food intake following microinjections of bombesin into the cerebral ventricles of male rats maintained at reduced body weight. All measurements of food intake and body temperature were recorded at an ambient temperature of 23 +/- 1 degrees C. The bombesin-induced hypothermia, but not the hypophagia, was partially reversed by prior subcutaneous injections of naloxone. Microinjections of bombesin failed to produce a decrease in body temperature in satiated rats.