David D. Avery

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.

The effects of bombesin injected into the anterior and posterior hypothalamus on body temperature and oxygen consumption

Abstract Bombesin was microinjected into the lateral ventricle, preoptic area, and posterior hypothalamus of cold-exposed rats. Preoptic and ventricular injections produced dose-dependent depressions in metabolism with subsequent hypothermia. Furthermore, injections into the preoptic area elicited greater depressions in body temperature than equivalent doses injected into the lateral ventricle. No changes in oxygen consumption or body temperature resulted from posterior hypothalamic administration of the peptide. The data suggest that the preoptic area may be an important site of action for bombesin and that bombesin-induced hypothermia is mediated, at least in part, by a reduction in metabolic rate.

A note on hair whorl position and cattle temperament in the auction ring.

The objective of this study was to further describe the relationships between facial hair whorls and temperament in cattle. Cattle (n=1636) from six commercial cattle auctions in Colorado and Texas were observed. Whorl location was classified according to lateral position (left, right, or middle) and height (high: above the top of the eye, middle: at eye level, low: below the bottom of the eye). A 4-point temperament score was used to rate each animal while it was in the auction ring. Cattle with a score of 1 remained calm and stood still or walked around, and those with a score of 4 were highly agitated and hit the ring fence, walls, partitions, or people with its head. The cattle observed were 75% Bos taurus beef breeds, 21% Holstein dairy cattle, 3% Bos indicus beef breeds, and 1% non-Holstein dairy breeds. Ten percent of cattle surveyed had no facial hair whorl, while 86% had a single spiral hair whorl, of which 47% had middle-middle whorl placement. Animals with a high whorl position or no hair whorl had higher temperament scores (P=0.01). Cattle with low whorls were more likely to have greater lateral displacement of whorls off of the centerline than cattle with high or middle whorls (P<0.01). Abnormally shaped whorls were more common on cattle with low whorls (P<0.01) and on cattle with lateral whorls located off of the centerline (P<0.01). Cattle with hair whorls on the centerline had more variable temperament scores (P=0.04). Beef cattle had more abnormal whorls than Holsteins (P<0.01). Temperament scores showed that Holsteins were calmer than beef cattle (P<0.01). Facial hair whorls in cattle may be a useful management tool in assessing which animals may become disturbed in novel environments.

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.

The effects of injections of bombesin into the cerebral ventricles on behavioral thermoregulation.

Abstract Bombesin is a potent hypothermic agent when administered centrally to animals maintained at environmental temperatures below thermoneutrality. At higher ambient temperatures, however, this peptide has been found to be ineffective in altering thermoregulation. Data are reported here which indicate that bombesin also alters thermoregulation at ambient temperatures at, or above, thermoneutrality. Bombesin was microinjected into the lateral ventricles of unrestrained rats trained to press a bar to escape radiant heat and receive a draft of 23 ± 1°C room air. Control injections did not alter the bar press response and rectal temperature rose an average of 2.4°C during the 30 min testing session. Following bombesin injections, however, the number of bar presses increased and body temperature did not rise above euthermic values. Additionally, animals which received bombesin were monitored at room temperature when they were removed from the apparatus after behavioral testing. These animals became hypothermic. The results are discussed in relation to the setpoint of body temperature. 1. 1. Bombesin 2. 2. Behavioral thermoregulation 3. 3. Setpoint 4. 4. Lateral ventricle.

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.

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.

The effects of tetraethyl lead on behavior in the rat

Abstract The behavioral effects on rats of various doses of tetraethyl lead, administered intragastrically, were measured on the following: bar press responding for food, two-choice discrimination under negative reinforcement, and emotional responses in the open field. Bar press response rates were drastically curtailed following administration of high doses of lead. Both trials to criterion and mean latency to criterion were detrimentally affected by administration of single doses of lead prior to acquisition of the discrimination. Lead had similar effects on these same measures in reversal of the original discrimination and in retention of the reversal. The performance deficits were not attributable to the tetraethyl radical; control injections of tetraethyl silane were without effect on all behavioral measures in the discrimination task. In addition, the results did not appear to be a function of emotional factors as lead did not influence trials to avoidance criterion or open field behavior. It was concluded that lead given intragastrically can impair learning and memory in the rat.

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.