Biomedical subjects

C J Billington

Publications and source records attributed to C J Billington.

At least 19 recordsLinked to original sources

PubMed1995

Buprenorphine increases intake of freely available and operant-contingent food in satiated rats.

Opiate administration increases short-term free feeding in satiated rats. The feeding effects of the mixed opioid receptor agonist/antagonist buprenorphine were examined in both free-feeding and operant chamber paradigms. Buprenorphine (0.1 and 0.3 mg/kg) produced significant increases in short-term free feeding (i.e., 4 h), an effect enhanced by repeated administration. Buprenorphine's effects on operant responding were examined in satiated rats using a fixed ratio (FR) 80 (initial pellet) FR 3 (subsequent pellets) reinforcement schedule. Buprenorphine (0.03-0.3 mg/kg) decreased latency to begin responding for food, and increased total number of pellets consumed in a 1-h session. Increases in food intake relative to control were caused by continued responding for food as sessions progressed. Naloxone suppressed both the free-feeding and operant-contingent intake induced by buprenorphine. Thus, buprenorphine increases both freely available and lever-press contingent food intake.

Animals↗

PubMed1995

Naloxone blocks that portion of feeding driven by sweet taste in food-restricted rats.

We evaluated the potency of naloxone on intake of normal and sweet chow in food-deprived and schedule-fed rats. We found that naloxone's anorectic potency was dependent on the type of chow presented to the rats and the deprivation schedule utilized to stimulate food intake. In 24-h and 48-h deprived rats, naloxone decreased intake of normal rat chow at doses ranging from 0.3 to 3 mg/kg. In chronically deprived rats (80% of normal body wt), these doses of naloxone failed to decrease intake of normal chow. Rats eating sweet chow ate more when energy deprived and were more sensitive than rats eating normal chow to naloxone-induced limitations in food intake, both in acute and chronic food-deprived groups. Thus naloxone decreased intake of sweet chow much more effectively than normal chow even when rats were chronically food deprived. We also found that an extremely low dose of naloxone (0.03 mg/kg) decreased intake of sweet chow by almost 50% in satiated rats.

Animals↗

PubMed1995

Cold-induced alterations in uncoupling protein and its mRNA are seasonally dependent in ground squirrels.

We were interested in determining whether season affects the ability of cold exposure to increase brown adipose tissue (BAT) thermogenic function in 13-lined ground squirrels after acute and chronic cold (4 degrees C) exposure. Tissues were collected from animals in April and September after cold exposure for 12, 24, or 48 h. Animals chronically exposed to the cold (10 days) were killed in early May and mid-August. We found that mitochondrial uncoupling protein (UCP) concentrations varied seasonally, with concentrations in control animals (at 23 degrees C) higher in late summer (mid-August and September) than in the spring (April and early May). Cold exposure in late summer did not induce further increases in UCP concentrations. In contrast, when animals were cold exposed in the spring, UCP concentrations and total UCP increased. Surprisingly, 10 days at 4 degrees C did not cause a greater increase in UCP concentrations than did 24 h at 4 degrees C. Chronic cold exposure increased the UCP mRNA-to-beta-actin mRNA ratio 48% in May, whereas a fivefold increase occurred in August. GDP binding was increased after 12 h at 4 degrees C in April; in contrast, animals attempted to hibernate when placed in the cold in September, and no increase in GDP binding was observed. Chronic cold exposure caused GDP binding to increase at both times. These results indicate that mitochondrial UCP concentrations are seasonally regulated in the 13-lined ground squirrel.

Acclimatization↗

PubMed1995

Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

Neuropeptide Y administered intracerebroventricularly and into the paraventricular nucleus of the hypothalamus stimulates feeding and decreases brown adipose tissue thermogenesis. Although specific neuropeptide Y antagonists are not yet available, previous studies had shown that the opioid antagonist naloxone blocked neuropeptide Y-induced feeding when both drugs were injected intracerebroventricularly. We wanted to find out if naloxone injected into specific brain sites would block neuropeptide Y effects on feeding and brown fat thermogenesis. Rats were double injected in specific brain sites with neuropeptide Y and either naloxone or naltrexone (a congener of naloxone). Food intake and brown fat measures were assessed. Naloxone or naltrexone in the paraventricular nucleus weakly decreased paraventricular nucleus neuropeptide Y-induced feeding and did not affect neuropeptide Y-induced reductions in brown fat activity. Peripheral naloxone blocked intracerebroventricular neuropeptide Y-induced feeding and brown fat alterations. Fourth ventricular naloxone decreased paraventricular nucleus neuropeptide Y-induced feeding, and naltrexone given into the nucleus of the solitary tract blocked paraventricular nucleus neuropeptide Y-induced alterations in feeding and brown fat. These data indicate that neuropeptide Y in the paraventricular nucleus may act on feeding and brown fat thermogenesis through opioidergic pathways in the nucleus of the solitary tract.

Adipose Tissue, Brown↗

PubMed1994

A review of GHRH stimulation test in psychiatry.

We critically reviewed controlled investigations of the growth hormone releasing hormone (GHRH) stimulation test in depression, anorexia nervosa, bulimia, panic disorder, schizophrenia, and Alzheimer's disease. Comparisons of GH responsiveness between patients and controls within each diagnostic category were equivocal and in some cases contradictory. Factors that may contribute substantially to the inconsistent findings within diagnostic categories include (1) the variability of GHRH-simulated GH among control groups; (2) the lack of uniformity in test procedures and outcome measures; and (3) the age and gender of subjects. In addition, the individual reproducibility of the GHRH stimulation test has not been adequately investigated and until the test's stability within subjects can be determined, the validity of interpretations resulting from the GHRH simulation test are in question.

Alzheimer Disease↗

PubMed1994

The effect of selective opioid antagonists on butorphanol-induced feeding.

Butorphanol tartrate (BT) potently stimulates food intake in satiated rats. The opioid receptor profile of BT is complex and is dependent upon the assay and animal species studied. In the present study we utilized three selective opioid antagonists; namely beta-funaltrexamine (beta-FNA), naltrindole (NTI) and norbinaltorphimine (nor-BNI), to probe the opioid receptor profile of BT as an orexigenic agent. Intracerebroventricular administration of nor-BNI (kappa) antagonized the feeding effects of BT (8 mg/kg, s.c.) at doses of 1, 10 and 100 nmol at the 1-2 h time point and decreased feeding at all time points for the 10 nmol dose. After 1 h, the 100 nmol dose of nor-BNI decreased BT-induced feeding by about 72%. In contrast, intraventricular injection of only the highest dose of the selective mu opioid antagonist, beta-FNA (50 nmol), decreased BT-induced feeding. Intraventricular administration of the delta opioid agonist, NTI, failed to alter BT-induced feeding at doses as high as 50 nmol. These data suggest that BT is dependent upon the kappa and perhaps the mu opioid receptors to increase food intake in satiated rats.

Animals↗

PubMed1994

Insulin, 2-deoxy-D-glucose, and food deprivation as discriminative stimuli in rats.

Using a two-lever drug discrimination procedure, two groups of four rats each were trained to discriminate the stimulus effects of 1.0 U/kg insulin or 125 mg/kg 2-deoxy-D-glucose (2-DG) from saline. A third group was trained to discriminate food deprivation produced by feeding 23 h prior to sessions from satiation produced by feeding 2 h prior to sessions. Differential responding was a direct function of dose or deprivation level in each group. Rats trained to discriminate insulin responded as if they had received insulin when they received 2-DG and vice versa. Insulin and 2-DG produced deprivation-appropriate responding in two of four rats trained to discriminate food deprivation. Low insulin and 2-DG doses produced drug-appropriate responding in rats deprived 47 h, but not in rats deprived 23 h. Blood glucose level was altered by the training doses of insulin and 2-DG, but not by 23-h deprivation. These results indicate that operations that induce feeding produce discriminable stimuli, and that these effects overlap or interact. Thus, drug discrimination procedures can be useful in the analysis of ingestive behavior.

Animals↗

PubMed1994

Butorphanol increases food-reinforced operant responding in satiated rats.

In the present series of studies we examined the effect of butorphanol tartrate on food-reinforced operant responding in satiated rats. In the first experiment, 8.0 mg/kg butorphanol was administered subcutaneously, once per day for 4 days, to satiated rats responding under an fixed ratio 10 (FR 10) reinforcement schedule. In the second experiment, butorphanol (0, 0.3, 1.0, 3.0, 10.0 mg/kg) was administered to satiated rats responding under an FR 80 (first pellet) FR 3 (subsequent pellets) reinforcement schedule for 4 consecutive days. Repeated butorphanol administration increased total amount of food consumed over sessions in both experiments. Under the FR 80 schedule component, butorphanol initially increased latency to acquire the first pellet, an effect attenuated by repeated administration. Whereas vehicle administration was associated with consumption of relatively large quantities of food within the first 10 min of receiving the first pellet, butorphanol was associated with continued feeding as the session progressed. These data suggest that butorphanol-induced food intake is associated with maintenance rather than initiation of feeding.

Animals↗

PubMed1994

Naloxone's effects on operant responding depend upon level of deprivation.

Naloxone's effects on initiation, maintenance, and maximal response effort to acquire food were examined in rats maintained under different levels of food deprivation. In Experiment 1, naloxone was administered SC to rats responding under an FR 80 (first pellet) FR 3 (subsequent pellets) reinforcement schedule. Naloxone did not increase time to acquire the first pellet. Naloxone's suppression of subsequent intake and lowest effective dose were inversely related to level of deprivation. In Experiment 2, rats responded for food under a Progressive Ratio 2 reinforcement schedule. Breakpoint was lowered only when rats were maintained with free access to food. Decreases in response and running rate were inversely related to deprivation level. Results are consistent with the hypothesis that opioids are involved in the maintenance but not the initiation of feeding.

Animals↗

PubMed1994

Methadone and feeding: sources of differences between home cage and operant chamber assessment procedures.

Methadone administration is reported to increase food intake in studies examining free feeding and to decrease food reinforced operant responding. In light of this apparent paradox, the present study evaluated methadone's effects on food reinforced operant responding under conditions more typical of free feeding studies than operant studies. The effect of methadone (5 mg/kg) on food intake was examined in rats maintained at 100% of their free feeding weights. Methadone did not increase food intake with food available under a fixed ratio 1 (FR 1) reinforcement schedule. Methadone did not alter response rate when each lever press produced a larger reinforcer (225 mg as opposed to 45 mg), but did increase food intake. When response requirements were changed from lever pressing to interruption of an infrared beam, increases in food intake following methadone administration were observed. Thus, the differences between methadone's effects on free feeding vs. operant chamber food intake may be due to procedural factors such as magnitude of reinforcement and response requirements.

Animals↗

PubMed1994

Preference and diet type affect macronutrient selection after morphine, NPY, norepinephrine, and deprivation.

The orexigenic agents morphine, neuropeptide Y (NPY), and norepinephrine (NE) and deprivation have been reported to induce selection of specific macronutrients: fat, carbohydrate (CHO), CHO, and fat, respectively. We utilized analysis of covariance to compensate for the influence of baseline preference on feeding induced by six experimental procedures: morphine, NPY, NE, 24 and 48 h food deprivation, and chronic dietary restriction. Rats received one of two dietary regimens: three macronutrient diets containing CHO, protein, or fat (regimen I) and two nutritionally complete diets that were high CHO or high fat (regimen II). Baseline preference significantly influenced dietary selection after all six experimental procedures studied in regimen I and after NPY, NE, 48 h food deprivation, and chronic dietary restriction in regimen II (covariate P < 0.05). In both dietary regimens, morphine (5 mg/kg) increased consumption of fat, NPY (5 micrograms icv) increased selection of CHO, and consumption of all diets was induced equally after NE injections (20 micrograms icv). After 24 or 48 h food deprivation, animals consumed more fat in regimen I and more CHO diet in regimen II. Restricting food intake by 20% increased fat and protein consumption in regimen I but had no effect in regimen II. Diet selection is affected by prior preference, feeding stimulus, and type of diet choice presented.

Analysis of Variance↗

PubMed1994

Rat hypothalamic NPY mRNA and brown fat uncoupling protein mRNA after high-carbohydrate or high-fat diets.

We measured the influence of diet composition on hypothalamic neuropeptide Y (NPY) message and brown fat uncoupling protein (UCP) mRNA using different diets. Sprague-Dawley rats ate ad libitum either chow, a high-carbohydrate (HC), an intermediate-carbohydrate (IHC), a high-fat (HF), or an intermediate-fat (IHF) diet, all with equal protein content (g/kcal). The HF and IHF groups ate less food mass and, except for HC, all groups consumed similar kilocalories during the study. After 1 wk, we killed the animals and extracted total RNA from arcuate nucleus, cortex, and brown adipose tissue (BAT). Arcuate NPY mRNA in the HF group was significantly (P < 0.001) lower than in the HC and chow group. There were no differences between groups in NPY message in cortex or NPY protein in the paraventricular nucleus. BAT UCP message levels were significantly higher (P = 0.001) in the HF group. Thus HF compared with HC and chow diet reduces expression of NPY mRNA in hypothalamic nuclei and increases expression of BAT UCP message.

Adipose Tissue, Brown↗

PubMed1994

Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism.

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN:1) NPY (1 micrograms/1 microliters injection) and ad libitum food; 2) NPY (1 micrograms/1 microliters injection) and food restricted to control intake; 3) saline injection (1 microliter) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, four groups of seven rats had NPY injected into the PVN:0 (vehicle control); 0.1 microgram; 0.5 microgram; and 1 microgram. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1993

The effect of norbinaltorphimine, beta-funaltrexamine and naltrindole on NPY-induced feeding.

The non-selective opioid receptor antagonist naloxone decreases the robust feeding observed after i.c.v. injection of neuropeptide Y (NPY). In the present study we evaluated the effects of three selective opioid receptor antagonists on NPY-induced feeding. Graded doses of norbinaltorphimine (norBNI), beta-funaltrexamine (beta-FNA) and naltrindole (NTI), antagonists of the kappa, mu and delta receptors respectively, were preinjected (i.c.v.) in male rats prior to injection of 5 micrograms NPY (i.c.v.). Food intake was measured 1, 2 and 4 h post-NPY injection. Injection of beta-FNA and norBNI were most effective in reducing NPY-induced feeding, whereas NTI had little effect on NPY-induced feeding.

Animals↗

PubMed1993

Effects of neuropeptide Y on ingestion of flavored solutions in nondeprived rats.

Recent evidence suggests that in addition to altering energy balance, neuropeptide Y (NPY) may stimulate ingestive behavior by modifying the orosensory quality of ingested substances. The present experiments investigated the effect of intracerebroventricular administration of NPY (5 micrograms/5 microliters) on ingestion of various flavored solutions in nondeprived rats. Experiment 1 examined the effects of NPY on ingestion of a range of concentrations of saline, sucrose, and saccharin solutions in single-bottle tests. Results indicated that NPY stimulates ingestion of both sucrose and saccharin solutions that are normally palatable. In Experiment 2, palatable sucrose solutions flavored with either orange or black cherry Kool-Aid for separate training groups were selectively associated with NPY injection during single-bottle training sessions. Subsequent two-bottle preference tests showed a significant shift in preference toward the flavor paired with NPY during training. The results of these experiments extend previous findings by showing that NPY can stimulate ingestion of sweet solutions regardless of caloric value and may potentiate sweet taste preference via an associative mechanism.

Animals↗

PubMed1993

Naloxone's anorectic effect is dependent upon the relative palatability of food.

It has been suggested that opioids modify food intake by enhancing palatability. In the present series of studies we evaluated the effect of naloxone on food intake of a preferred food (chocolate chip cookies), normal rat chow, and an "aversive" food (high fiber chow). We found that naloxone decreased 18- and 48-h deprivation-induced intake of chocolate chip cookies much more potently than that of chow, when these foods were presented on separate occasions. When these foods were presented concurrently, this difference in naloxone's potency was no longer apparent. When rats were offered high fiber chow, only the 10 mg/kg dose of naloxone decreased intake. In these same rats naloxone significantly decreased normal chow intake at a dose of 0.1 mg/kg. Thus, naloxone's ability to decrease food intake appears to be dependent upon the palatability of the food.

Animals↗

PubMed1992

Effects of methadone on free feeding in satiated rats.

A variety of opioids and opiates are known to increase short-term food intake. In the present study, we evaluated the effects of methadone on free feeding in satiated rats. We assessed the effect of methadone (0, 1.5, 3.0, 5.0, and 10.0 mg/kg) on food intake 1, 2, 4, and 6 h after injection for 3 consecutive days. Two hours after methadone administration, food intake was inversely related to dose, but after 6 h a direct relationship between dose and feeding was obtained. Food intake increased with repeated methadone administration. In Experiment 2, methadone (5.0 mg/kg) was injected and food was made available 0, 1, 2, or 3 h later. Maximal food intake occurred in the third and fourth hours following methadone administration. As in Experiment 1, food intake increased with repeated methadone administration. Increases in food intake following repeated methadone administration may have been due to the development of tolerance to effects of methadone that may interfere with feeding, such as sedation. In Experiment 3, methadone was administered daily or every fifth day, assuming that spacing injections would retard tolerance development. Repeated daily methadone administration was associated with increased food intake earlier in the session, whereas increases in food intake following spaced methadone administration occurred later in the session. These data indicate that methadone increases short-term feeding in satiated rats. This is in contrast to the reported decrease in food-reinforced behavior noted in operant studies. This contrast may be due to sedating or other disabling effects of methadone.

Animals↗

PubMed1992

Hypothalamic neuropeptide Y regulation of feeding and energy metabolism.

Neuropeptide Y is an important regulator of energy intake and expenditure. The central portion of this regulatory system appears to reside in the arcuate nucleus/paraventricular nucleus of the hypothalamus. The effects of neuropeptide Y on energy metabolism include increased food intake, decreased thermogenesis and increased white fat storage.

Animals↗