Richard L. Sprott

Genetic mechanisms of drinking and feeding

Abstract The literature on the genetics of feeding and drinking, and the genetic methods that will be useful for future research, are described. Four subjects which have been studied most thoroughly by geneticists are discussed: intake of plain water, intake of and preference for flavored water, body weight and food intake regulation when confronted with high-fat diets, and excess body weight. Although a moderate number of strain comparisons and a few genetic analyses have been reported, relatively little is known about the nature of genetic influences. The only major exception is the study of obese mutants where considerable progress has been made in elucidating the physiological mechanisms which produce overeating in such animals. However the study of the behavioral changes in obese mutants is still at an early stage.

Genetic analysis of schedule induced polydipsia

Abstract Susceptibility to schedule induced polydipsia (SIP) was assessed in mice of the C57BL/6J and DBA/2J strains, in the F 1 hybrid between these two strains, and in three segregating generations. The results provided clear evidence that susceptibility is inherited. Two alleles have been demonstrated; Sip d , the dominant (susceptible) allele, and Sip b , the recessive (nonsusceptible) allele.

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

Abstract 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.

Diet/taste and feeding behavior of genetically obese mice (C57BL/6J-ob/ob).

Eleven experiments on lean (C57BL/6J) and obese (C57BL/6J-ob/ob) mice were conducted to examine the effects of diet/taste manipulations on the food and fluid intake of obese mice. Although normally hyperphagic, obese mice consumed less of a milk diet than did lean mice, when the diet was initially introduced and when the milk was adulterated with quinine. However, in a second and third experiment in which degree of food deprivation was controlled, obese and lean mice responded similarly to the addition of quinine to sweetened condensed milk. Obese and lean mice responded similarly to variations in the sweetness of milk solutions but obese mice sometimes underresponded to variations in the sweetness of plain water. Obese mice regulated caloric intake fairly accurately when corn oil or lard was added to their diet. Obese mice showed a higher preference for corn, safflower, peanut, and olive oils versus solid food than did lean mice but both groups decreased oil preference following food and oil deprivation and increased oil preference following oil deprivation.

Operant performance in inbred mice

The procedures described in this report are standard operant procedures, which have been used successfully to condition mice to barpress for a food reward on a variety of schedules of reinforcement. The schedules of reinforcement include continuous reinforcement, nine fixed ratio values, and six fixed interval values. Mice of five genotypes have been exposed to some or all of these schedules. Performance was typical of that observed in other organisms, and satiation was not a problem in sessions lasting from 2 to 31/2 h. This experiment clearly demonstrated that barpress performance can be obtained with inbred mice as readily as with other organisms.

The influence of mouse genotype on passive avoidance learning and subsequent concentrations of norepinephrine and serotonin in the hypothalamus and hippocampus

Subjects from two strains of mice, C57BL/6J and DBA/2J, were either trained in a passive avoidance task or served as shock controls by receiving footshock at the same time as animals being trained. DBA/2J mice reached the learning criterion significantly faster than C57BL/6J mice. Latencies to leave the “safe” area on the first trial were not significantly different between the two strains. Subsequent analyses of the results of the spectrophotofluorometric assay of norepinephrine and serotonin in the hypothalamic and hippocampal brain regions revealed two effects. First, hippocampal serotonin was higher in DBA/2J mice compared to C57BL/6J mice. Secondly, hypothalamic norepinephrine was higher in DBA/2J mice trained for passive avoidance than in DBA/2 J mice that served as shock controls. The results suggest that the higher levels of hippocampal serotonin in DBA/2J mice compared to C57BL/6J mice may predispose the former strain to show better passive avoidance performance under specified circumstances. The observed differences in norepinephrine may have resulted from an interaction between serotonin levels and exposure to the present learning situation.

Regulation of caloric intake in yellow mice (C57BL/6J-Ay/a)

Abstract The ability of yellow and normal black mice to reduce food intake when given surplus calories was studied to elucidate the mechanisms responsible for hyperphagia in yellow mice. When given sugar solutions to drink, immature (6–7 weeks old) yellow mice increased total caloric intake more than did lean control mice. Older (11–14 weeks) yellow mice were similar to control mice. The oldest yellow mice tested (25–33 weeks) increased total caloric intake less than lean control mice, when given sugar solutions. In contrast, yellow mice of all ages increased total caloric intake more than lean mice when given corn oil. Yellow mice had similar or lower preference for sugar and oil calories than did black mice.

Food intake and body weight regulation in diabetes (db/db) and obese (ob/ob) mice.

Diabetes and lean control mice of two strains (C57BL/6J and C57BL/KsJ) were tested for their ability to regulate food intake and body weight when subjected to caloric deficits and surpluses. Diabetes mice regulated food intake and body weight as well as or better than control mice when given milk solutions to drink. Recovery from food deprivation was impaired in older (more than 13 weeks of age) but not in younger (8 weeks of age or less) diabetes and obese (C57BL/6J-ob/ob) mice. These results suggest that overweight itself is responsible for some of the behavioral disturbances in genetically obese mice.