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Biomedical subjects

R B Kanarek

Publications and source records attributed to R B Kanarek.

At least 19 recordsLinked to original sources

Hormonal milieu affects tailflick latency in female rats and may be attenuated by access to sucrose.

The steroid hormones estrogen (E) and progesterone (P) are known to modify pain sensitivity; however, the relative role of each of these hormones in this process is not well understood. To systematically investigate the effects of E and P on nociception, pain sensitivity was assessed under several hormone conditions. Tailflick (TF) latencies were measured every other day in 10 cycling female rats and 10 female rats during luteal functioning (pseudopregnancy). Thirty ovariectomized (OVX) rats were tested for TF latency following administration of 10 micrograms estradiol benzoate (EB) and either 0.0, 0.5, or 1.0 mg of P. Significant differences in TF latency were seen across days of the estrous cycle but not during luteal functioning. Tailflick latencies during luteal functioning were elevated relative to latencies in normally cycling animals. Among OVX rats, those administered EB and P (1.0 mg) displayed significant reductions in TF latency compared to vehicle controls. As a separate line of research indicated that consumption of highly palatable foods modified pain sensitivity, whether chronic sucrose consumption might overide the influence of hormones on nociception was examined. Ovariectomized rats given EB and P (0.0, 0.5, or 1.0 mg) were allowed chronic exposure to a 32% sucrose solution. Our preliminary findings suggest that chronic sucrose consumption attenuates hormonally induced differences in nociception.

Animals

Dietary influences on the acute effects of anorectic drugs.

The effects of acute administration of d-amphetamine sulfate (0.0, 0.5, 1.0 and 2.0 mg/kg) and dl-fenfluramine hydrochloride (0.0, 1.5, 3.0 and 6.0 mg/kg) on food intake were examined in male Sprague-Dawley rats fed either a high-carbohydrate diet (carbohydrate equaled 65% of total calories) or a high-fat diet (fat equaled 65% of total calories). Animals were given ad lib access to the diets throughout the experiment. Drug injections were given at 0900 on experimental days and food intakes were measured at 1, 3 and 6 h postinjection. Amphetamine led to dose-related decreases in food intake for animals on both diets. The effects of amphetamine were most noticeable at 1 and 3 h postinjection. No differences in amphetamine's effects on food intake were found as a function of diet. Fenfluramine injections also led to dose-related reductions in food intake for animals in both dietary conditions. In contrast to amphetamine, however, fenfluramine led to greater reductions in food intake for rats fed the high-fat diet than for rats fed the high-carbohydrate diet. These data demonstrate that dietary variables must be considered when evaluating the anorectic actions of psychopharmacological agents.

Animals

Dietary influences on morphine-induced analgesia in rats.

Morphine-induced analgesia was examined using a tail-flick apparatus in 36 adult male Sprague-Dawley rats. Rats were given ad lib access to Purina Chow alone (N = 9) or given a choice of Purina Chow and either a 0.15% saccharin solution (N = 9), a 32% sucrose solution (N = 9), or hydrogenated vegetable fat (Crisco) (N = 9). Analgesic testing was conducted immediately preceding and at 30, 60 and 90 minutes following intraperitoneal administration of morphine sulfate (0.0, 2.5, 5.0 and 10.0 mg/kg). No differences in analgesic responsiveness were observed as a function of diet preceding morphine administration. However, dietary variables did alter morphine-induced analgesia. At 30 minutes following injections of the highest dose of morphine, animals fed saccharin, sucrose or Crisco had significantly longer tail-flick latencies than rats given only Purina Chow. Sixty minutes following injections, rats fed Crisco continued to display a significantly longer tail-flick latency than rats fed only Chow. These data demonstrate that palatable substances can enhance the analgesic properties of exogenous opioids.

Animals

Dietary modulation of the anorectic potency of amphetamine.

The effects of intake of an amphetamine solution on food and fluid intakes, body weight (b.wt.) and feed efficiency (FE) were examined in rats fed either a high-carbohydrate (HC) (65% of total calories) or high-fat (HF) (65% of total calories) diet. During a 17-day predrug period, neither caloric intake, fluid intake, b.wt. nor feed efficiency (FE) differed as a function of diet. When given a 0.1 mg/ml amphetamine sulfate (AMPH) solution as their sole source of fluid, rats in both diet groups decreased fluid intake by an equivalent amount. While diet did not influence AMPH intake, it did alter the drug's effects on caloric intake, b.wt. and FE. In both diet groups, rats drinking AMPH decreased caloric intake, b.wt. gain and FE relative to rats which drank water. However, rats fed the HC diet decreased caloric intake less, but lost more weight than rats fed the HF diet. Further, rats fed the HC diet displayed a rapid tolerance to the anorectic effects of AMPH, with no tolerance to the drug's effect on b.wt. In contrast, rats fed the HF diet suppressed caloric intake throughout the drug period, but weighed more than rats fed the HC diet. Thus, when drinking the AMPH solution, FE of rats fed the HC diet was significantly lower than that of rats fed the HF diet. When the drug was removed, rats eating the HC diet failed to alter caloric intake and b.wt. In contrast, rats fed the HF diet increased caloric intake and gained weight. These data indicate that dietary factors must be considered when evaluating the anorectic actions of psychopharmacological agents.

Amphetamine

Diet selection following a chronic morphine and naloxone regimen.

Total caloric intake and patterns of dietary self-selection of the three macronutrients, protein, carbohydrate and fat, were examined in adult male rats maintained on a 6-hr feeding schedule following daily injections of morphine (10 mg/kg), naloxone (1 mg/kg), the two drugs together, and saline. Animals received drug injections for 10 consecutive days. All animals received saline injections for the 5 days preceding and 5 days following the experimental period. Naloxone injections led to a significant reduction in total caloric intake. Neither morphine nor morphine and naloxone together significantly affected total caloric intake. Each of the drugs had a distinct effect on macronutrient selection. Morphine produced a significant increase in fat intake and decrease in carbohydrate intake, while naloxone led to a slight reduction in fat intake. When the two drugs were given together, a significant elevation in carbohydrate intake and reduction in fat intake were observed. Protein intake was not affected by any of the drugs. These results are discussed with respect to the hypothesized role of the endogenous opioid system in the regulation of energy balance.

Animals

Effects of food snacks on cognitive performance in male college students.

The effects of food snacks consumed in the late afternoon on cognitive performance in college-aged men were investigated in two experiments. The effects of the snacks were tested in the same subjects after they either consumed or skipped lunch. In the first experiment, the calorie-rich snack was a confectionery product, while in the second experiment, the snack was fruit-flavored yogurt. In both experiments, performance on cognitive tasks following consumption of the calorie-rich snack was compared to performance following consumption of a very low calorie snack (lemon-lime flavored diet soda without caffeine). Four cognitive tasks were employed: digit span recall (forward and backward), arithmetic reasoning, reading, and attention. In both experiments, subjects recalled significantly more digits in the backward digit span test and responded significantly faster in the attention task when they had consumed the calorific snack than when they had consumed the diet soft drink. Additionally, in Experiment 2, subjects solved significantly more arithmetic problems and solved these problems in significantly less time after eating a fruit-flavored yogurt than after consuming the diet soft drink. Results of these experiments suggest that a late afternoon energy-containing snack can have positive effects on cognitive performance on tasks that require sustained attention.

Adult

Insulin modifies flavor aversions and preferences in real- and sham-feeding rats.

In separate, parallel experiments, rats were allowed to sham or real feed a flavored sweetened condensed-milk solution after a 17.5-h fast. Coinciding with administration of the milk were injections of insulin or vehicle (saline). Insulin had no effect on intake in the real feeding situation, and flavors paired with insulin (0.8, 2.5, or 5.0 U/rat) were avoided, relative to saline-paired flavors. In sham-feeding rats, insulin (0.8 U/rat) significantly reduced the amount of milk consumed, and flavors paired with insulin injection were preferred, relative to saline-paired ones. Insulin produced a relatively larger hypoglycemia during sham feeding than during real feeding. Thus it appears that insulin-paired flavors of milk may be preferred by animals when they are ingested in sham feeding but not in animals real feeding. Perhaps rapid gastric emptying, as would occur with a liquid diet, accompanied by increased insulin levels, leads to malaise and flavor aversion.

Animals

Selection of protein and fat by diabetic rats following separate dilution of the dietary sources.

Diabetic and normal rats were allowed to select their diets from separate sources of protein, carbohydrate and fat. Following the determination of baseline intakes, diabetic and normal rats received dietary components in which either the protein (Experiment 1) or fat source (Experiment 2) was diluted by 25% or 50% by the addition of cellulose. Diabetic rats failed to maintain protein intake at both dilution levels, but made up for the loss of protein-derived calories by consuming more fat. Diabetic rats maintained fat intake at both dilution levels. Dietary dilutions had no effect on total caloric intakes or body weight gain of diabetic rats. Diabetic status, measured by fasting plasma glucose levels and urinary glucose excretion rates, also was unaffected by diet dilutions. These data suggest that diabetic rats maintain total caloric intake following dilution of either the protein or fat source of their diets, but defend intake of fat-derived calories more readily than protein-derived calories. Normal rats maintained both protein and fat intake at the 25% but not at the 50% dilution level. These findings are discussed in terms of the ability of diabetic rats to solve the metabolic problems associated with their diabetic condition.

Animals

Dietary modulation of oral amphetamine intake in rats.

The interaction of sucrose availability and oral self-administration of amphetamine was examined in 23 male Sprague-Dawley rats. Fourteen rats were given a 0.075 mg/ml amphetamine sulfate solution as their sole source of fluid and 9 rats were given water. Feeding conditions were alternated between weeks with both granulated sucrose and chow available and weeks with only chow present. Rats drank significantly less of the amphetamine solution when consuming sucrose and chow than when eating chow alone. Sucrose intake had a slight effect on water intake. Rats drinking the amphetamine solution consumed significantly less food, gained significantly less weight, and were significantly less efficient at using calories for weight gain than rats drinking water. However, when given access to sucrose, rats drinking the amphetamine solution chose a significantly greater proportion of their daily caloric intake as sucrose (60%) than rats drinking water (42.5%). The present results demonstrate that 1) amphetamine intake alters nutrient choice and 2) that dietary variables can profoundly affect drug self-administration.

Administration, Oral

Peripheral serotonin administration selectively reduces fat intake in rats.

Recent research has led to the hypothesis that serotonergic mechanisms may be involved in both the control of energy intake and appetites for specific nutrients. Most of this research has focused on serotonin (5-HT) within the central nervous system. However, there is evidence which suggests that peripheral 5-HT also may be involved in the control of energy intake and nutrient selection. To further assess this suggestion, the effects of peripheral 5-HT administration on energy consumption and nutrient intakes were examined in adult male Sprague-Dawley rats given separate sources of protein, fat and carbohydrate. Administration of 5-HT (doses ranging from 2-6 mg/kg) led to significant dose-related decreases in total energy intake in both freely feeding and food-restricted rats. Examination of individual nutrient intakes revealed that following 5-HT, fat intake was more suppressed than either carbohydrate or protein intakes. Administration of the 5-HT antagonist, methysergide, blocked the suppressive effects of 5-HT on both total energy intake and fat intake. The present data support the proposal that peripheral serotonergic mechanisms play a role in ingestive behaviors.

Animal Feed

Factors influencing the effects of nutritive and non-nutritive sweeteners on energy intake and body weight in rats.

During the past 10 years, a variety of roles have been proposed for carbohydrates in the control of food intake and body weight. Carbohydrate consumption has been associated with (1) elevations in body weight and (2) alterations in macronutrient selection. However, work reviewed in this paper demonstrates that a number of factors including carbohydrate composition and other nutrients in the diet can moderate the effects of carbohydrates on energy intake, nutrient selection and body weight.

Animals

Sucrose-induced obesity: effect of diet on obesity and brown adipose tissue.

Adult male Sprague-Dawley rats were divided into three groups and fed diets containing either 10, 20, or 40% protein for 56 days. Half of the rats in each dietary condition were given a 32% sucrose solution plus the standard diet and water. Sucrose intake varied directly as a function of dietary protein levels. Rats fed either the 10 or 20% protein diet and sucrose had higher caloric intakes, gained more weight, were more efficient at using calories for weight gain, and had more adipose tissue than rats given the same diet without sucrose. Rats fed the 40% protein diet and sucrose did not exhibit overeating, excess weight gain, or increased feed efficiency relative to animals fed the 40% diet alone. Animals given sucrose had more interscapular brown adipose tissue (IBAT) and a greater metabolic potential for thermogenesis in IBAT as determined by GDP binding in mitochondria than rats not fed sucrose. These results demonstrate that dietary protein is important in the development of sucrose-induced obesity and that increases in IBAT mass and activity can occur concomitant with increased feed efficiency.

Adipose Tissue, Brown

Maternal malnutrition in the rat: effects on food intake and body weight.

The effects of dietary protein level on food intake and body weight were examined in adult female rats during a 35-day pre-mating period and during gestation and lactation. During the pre-mating period, no differences in daily food intake were observed among rats fed a 6% casein, 8% casein or 25% casein diet. However, during this period, rats fed the 6% casein diet gained significantly less weight than those with ad lib access to the 8% or 25% casein diets or than rats pair-fed the 25% casein diet in amounts equivalent to that consumed by rats in the 6% or 8% casein groups. Additionally, rats fed the 6% casein diet displayed decreased efficiency of energy utilization, calculated as weight gain per 100 kilocalories consumed, relative to rats fed the 8% or 25% casein diets. No differences in food intake were observed among the groups during gestation. However, rats fed the 6% casein diet gained less weight than rats fed the 8% or 25% casein diets. During lactation rats fed either the 6% or 8% casein diet consumed significantly less food than animals given the 25% casein diet ad lib. During the second week of lactation, rats receiving ad lib access to the 25% casein diet gained weight while those receiving the 6% or 8% casein diets continued to lose weight. At parturition, body weights of pups did not differ as a function of dietary condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Central and peripheral contributions of endogenous opioid systems to nutrient selection in rats.

The contribution of central and peripheral sites to opioid mediation of energy intake and dietary self-selection of the three macronutrients, protein, fat, and carbohydrate, was examined in male rats. Animals given access to either Purina Chow or a self-selection regime were injected with either the opioid antagonist, naltrexone (0.0, 0.1, 1.0, and 5.0 mg/kg, IP), or quarternary naltrexone (0.0, 0.1, 1.0, and 5.0 mg/kg, IP), an opioid antagonist that does not readily enter the central nervous system. Animals received injections at the beginning of an 8-h feeding period, and nutrient intakes were measured at 1, 2, 4, and 8 h postinjection. Naltrexone and its quarternary analogue differed in their effects both on total energy intake and macronutrient selection. Naltrexone led to significant decreases in total energy intake in animals on both dietary regimes, whereas quarternary naltrexone did not modify energy intake of animals given access to either diet. Naltrexone produced a sustained reduction in fat intake and initial decreases in carbohydrate and protein intakes. Quarternary naltrexone did not modify overall energy intake but did lead to modifications in nutrient choice. In contrast to naltrexone, quarternary naltrexone resulted in increased fat intake, decreased carbohydrate intake, and a small reduction in protein intake. These data suggest that both peripheral and central sites contribute to opioid effects on patterns of nutrient choice.

Animals

Preoperative experience with insulin enhances glucoprivic feeding in rats with lateral hypothalamic lesions.

Adult male Sprague-Dawley rats received either one injection per week of regular insulin (IP, 5 Units) or saline for 4 weeks prior to destruction of the LH or sham-operations. During this preoperative period, animals given insulin consumed significantly more food in a 6-hr test period than animals given saline. Following surgery, animals were given 3 weeks to recover from the acute effects of LH lesions and then tested for responsiveness to glucoprivic challenges. Sham-operated animals from both pre-operative injection groups consumed significantly more food during a 6-hour period when injected with either insulin (5 and 7.5 Units) or 2-DG (400 mg/kg) than when given saline injections. Similarly, LH-lesioned rats with preoperative experience with insulin significantly increased food intake when given insulin or 2-DG. In contrast, LH-lesioned rats without preoperative experience with insulin failed to increase feeding in response to the administration of either insulin or 2-DG. Differences in feeding responses following glucoprivation between LH-lesioned rats with and without preoperative exposure to insulin were not a function of differences in the extent of central nervous system damage. The present data indicate that experimental conditions play an important role in determining the presence or absence of regulatory deficits following brain damage.

Animals