Effects of the dopamine D1 receptor antagonist SCH 39166 on the ingestive behaviour of alcohol-preferring rats

The present study evaluated the effect of the selective and long-acting dopamine D₁ receptor antagonist SCH 39166 on several aspects of the ingestive behaviour of genetically selected alcohol-preferring rats, bred from Sardinian alcohol-preferring rats. The effect of subchronic (8 days) subcutaneous drug administration was evaluated on the simultaneous daily intake of 10% ethanol, food and water. SCH 39166, 0.1 mg/kg, did not significantly modify the intake of the three ingesta. The dose of 1 mg/kg differentially modified rat ingestive behaviour, inhibiting intake of 10% ethanol, without modifying total fluid and food intake. The higher dose of 5 mg/kg produced a non-selective suppression of ingestive behaviour, which was accompanied by behavioural impairment. Acute drug injection was tested on 2-h intake of 10% sucrose, 0.1% saccharin, water or food. The doses of 0.1 and 1 mg/kg markedly inhibited the 2-h intake of 10% sucrose and 0.1% saccharin, but they did not modify either the 2-h water intake in water deprived and water sated rats or the 2-h food intake in food deprived rats. These findings suggest an important role of mechanisms mediated by D₁ receptors in the control of alcohol and sweet solution intake, but not in water and food intake. Moreover, they indicate that SCH 39166, in relation to its selectivity and long-lasting activity, is an interesting pharmacological tool to investigate further the role of D₁ receptor mechanisms in the control of ingestive behaviour.     

Genetic influences on saccharin preference of mice

Preference for a 0.1% solution of sodium saccharin was assessed in a two-bottle, saccharin versus water, preference test. Animals were adult mice from four inbred strains (BAlb/cJ; C57BL/6J; I^s/Bi; 101BAg/Rl), both reciprocal F₁ crosses of BAlb with C57, and a hetergeneous generation formed by crossing F₁ with wild trapped mice. Individuals from the 101 strain demonstrated no preference for saccharin or water while the other inbred strains preferred saccharin. No sex or maternal effect was detected. Heritability (h²) and coefficient of genetic determination (CGD) was estimated by alternative methods. The CGD was between 0.81 and 0.94 ± 0.024; h² = 0.55 to 0.68. This high degree of genetic involvement suggests that genotype is a major determinant of individual differences in saccharin preference.     

Hunger and satiety in genetically obese mice (C57BL/6J-ob/ob)

To determine the mechanism for hyperphagia in genetically obese mice (C57BL/6J-ob/ob), several experiments were conducted on the ability of these mice to respond to caloric deficits and surpluses. Presentation of food or sugar reduces subsequent operant licking in both obese and lean mice. When given sugar solutions, evaporated milk, or sweetened non-fat milk, both obese and lean mice reduce food intake to compensate for the calories obtained from the solutions. These findings indicate that genetically obese mice respond normally to caloric surpluses. Obese mice respond to food deprivation (caloric deficit) by increasing subsequent food intake but they do so more slowly than controls.     

Alterations in ingestive behavior following experimental portacaval anastomosis in rats

Following surgical construction of an end-to-side portacaval shunt (PCS), male rats exhibited exaggerated consumption of glucose, saccharin, saline, and ethanol solutions relative to sham-operated rats in 24-hr preference tests with water present. Spontaneous daily water intake was also increased, but daily food intake and body weight were decreased by PCS. The overconsumption of glucose, saccharin, and saline exhibited by rats with portacaval shunts was reduced, or eliminated, by providing a corn supplement to their diet, consistent with the view that the disturbance of amino acid balance may have contributed to this ingestive abnormality. In a series of short drinking tests, rats with portacaval shunts consumed more of both 10% glucose and 10% fructose (given in separate tests) than sham-operated rats and glucose intake was greater than fructose intake for both of these groups. However, neither surgical nor saccharide condition affected the duration of the first bout or the initial inter-bout interval, indicating that the relative satiating properties of these two monosaccharides were probably not altered by portacaval shunting.     

The effect of postconditioning CS experience on recovery from radiation-induced taste aversion

Seventy-two hours after saccharin (CS) was paired with either a 100R or sham radiation exposure, rats received a 0-, 3-, 6-, 12-, 24-, or 46-hour saccharin-alone presentation followed by a 23-hour two-bottle preference test. Generally, faster recovery from the aversion was observed in animals receiving longer CS-alone presentations. The present procedure differs from previous work done with other toxins in that animals were not fluid-deprived during the postconditioning period. This enabled animals to constantly control the volume, duration, and inter-bout interval of the saccharin drinking episodes independent of any experimentally imposed drinking schedule. In addition, the two-bottle test provided a sensitive measure of the status of the saccharin aversion following the saccharin-alone presentation.     

Disparity between formation of conditioned flavor aversions and neophobia during grooming in rats and mice

Mice (Mus musculus) allowed to groom a paste containing saccharin from their fur before injection with lithium chloride displayed a saccharin aversion in subsequent drinking preference tests. No attenuation of neophobia was observed in mice grooming saccharin because the animals failed to display a neophobia towards saccharin in drinking tests. Rattus norvegicus displayed neophobia towards saccharin in two- and single-bottle drinking tests but this neophobia was not attenuated by grooming experience with the saccharin paste. Rats apparently learn that if a taste is hazardous in the grooming context it is also likely hazardous in an appetitive context. Learned safety in grooming, however, does not generalize into the appetitive context. The results support the view that neophobia and learned taste aversion depend upon different mechanisms.     

Cephalic insulin response as a test for completeness of vagotomy to the pancreas

Rats received one of four surgical manipulations of the abdominal vagus; either a total vagotomy, a selective dorsal trunk vagotomy, a selective ventral trunk vagotomy or a sham operation. After recovery from the surgery, all rats were fasted overnight and given a saccharine solution the next day. Blood samples were taken 30 min prior to and 3 min after the sampling of the saccharin. Rats with the dorsal vagal trunk intact (those with either a sham lesion or with a selective ventral trunk lesion) had an elevation of immunoreactive insulin after drinking the saccharin whereas those with the dorsal vagal trunk severed did not. This simple procedure is recommended as a test for completeness of vagotomy to the pancreas since it is quick and easy to perform and since it is non-terminal and relatively non-invasive.     

Concurrent pentobarbital- and saccharin-maintained responding: effects of saccharin concentration and schedule conditions

Responses of rhesus monkeys were reinforced by delivery of either a pentobarbital (4.0 mg/ml) solution or a vehicle (water) or saccharin solution under a concurrent signaled differential reinforcement of low rates 30-s schedule. After 30 s of no responding, the first response on the pentobarbital or saccharin spout resulted in the delivery of the appropriate solution and reset the timing on both spouts (i.e. a mutually exclusive choice). In the first experiment, the concentration of saccharin was gradually increased across sessions. As saccharin concentration increased, pentobarbital deliveries decreased and saccharin as well as total session deliveries increased. In a second experiment, pentobarbital and 0.24 (mg/ml) saccharin were made available under concurrent signaled differential reinforcement of low rates 30-s schedules which operated independently. Under these conditions responding on one spout had no consequences with respect to the other spout. The reduction of pentobarbital deliveries was substantially attenuated when the choice was not mutually exclusive.     

Prenatal nicotine affects fetal testosterone and sexual dimorphism of saccharin preference

In order to study effects of nicotine on fetal gonadal axis and sexually dimorphic behavior, time-pregnant Sprague Dawley rats were implanted on gestational day (GD) 12 with an osmotic minipump containing either nicotine tartrate, tartaric acid or saline. Others were sham-operated on GD 12 or left untreated. Male fetuses of all control groups displayed the characteristic rise in plasma testosterone at GD 18 (as compared to GD 17 and 19); this was abolished by nicotine. Adult offspring of untreated or tartaric acid-treated dams exhibited a marked sexual dimorphism in their preference for saccharin-containing drinking water at 0.06-0.25%. No such sex difference was seen in offspring of nicotine-treated rats. In controls, the sexes differed with respect to the proportion of rats with high saccharin preference. In the group of males prenatally exposed to nicotine, the proportion of animals with high preference increased to the female level. These data indicate that prenatal exposure to nicotine can interfere with the development of the male gonadal axis and with the organization of sexually dimorphic behavior.     

Functional study of nasal mucosa in endoscopic sinus surgery and its correlation to electron microscopy of cilia

The effect of functional endoscopic sinus surgery (FESS) was evaluated in 20 patients with chronic sinusitis. The physiological function of sinus mucosa and its mucociliary transport mechanism was assessed pre and post operatively in patients undergoing FESS by performing Saccharin clearance test. The effect of functional sinus surgery on nasal mucosa was evaluated using scanning electron microscopy and study of the ultrastructure of cilia in pre and post operative patients and correlation with histopathological examination. The mucociliary transport mechanism of the sinus mucosa improved 6 weeks following surgery. Histopathologically there was evidence of improvement in the ciliary population and decrease in inflammation, ulceration, fibrosis, vascular congestion, edema, squamous cell metaplasia, basement membrane thickening and polyp formation in comparison to the diseased mucosa sampled preoperatively. Scanning electron microscopic examination revealed considerable increase in the ciliary area as well as the orientation of cilia. Subjective improvement 6 weeks following surgery was confirmed by decrease in saccharin test time. This study revealed that FESS is an effective surgical procedure in chronic sinusitis and improves the overall function of the sinuses