Jacques Le Magnen

The olfactory control of meal pattern in rats

Abstract The role of the olfactory input in the control system regulating the free food intake of rats has been investigated. In a first experiment it was shown that the mean daily intake of 20 adult male and female rats, made anosmic by the bilateral ablation of olfactory bulbs, did not change significantly after surgery. But, as a result of the bulbar removal, the day to day fluctuation of this daily intake was significantly increased. In a second experiment the pre and postoperative recording of the daily feeding pattern (meal size and intervals) revealed that the olfactory bulbs ablation induced a more or less persistant and typical nibbling pattern. The stereotaxic electrolytic lesion of the cortico-medial amygdaloid olfactory projection, interrupting one of the olfacto-hypothalamic pathways, induced the same disrupted feeding pattern. The results are discussed in relation to control systems regulating meal sizes and meal to meal intervals in normal rats. It is suggested that the orosensory and particularly the olfactory control is responsible for determining the normal feeding pattern made of large and consistant meals followed by long intervals of nonfeeding.

Decrease in ethanol consumption by naloxone in naive and dependent rats

Acute effects of the opiate antagonist, naloxone, on alcohol intake have been examined and compared in naive and behaviorally dependent rats. In naive rats the aversion to an 8% alcohol solution exhibited in a 30 min presentation was selectively augmented by an IP administration of naloxone (1 mg/kg) 30 min before a morning drinking session. In other rats, behavioral dependence was established by 15 days of IG administration of intoxicating doses of alcohol. This dependence was exhibited by a sustained preference for ethanol for 6 days. Naloxone (1 mg/kg) abolishes the acquired preference for ethanol tested during an 8 hour day time presentation. These effects of naloxone on alcohol intake in ethanol naive and dependent rats are interpreted in relation to a general non-specific action of naloxone on preferred or aversive flavoured solutions.

The different effects of continuous night and day-time insulin infusion on the meal pattern of normal rats: Comparison with the meal pattern of hyperphagic hypothalamic rats

Abstract The different night and day-time effects of continuous intravenous infusion of various doses of insulin on the meal pattern have been investigated in normal rats. In the day-time a dose-response curve was apparent. An 86–220% increase in the 12 hr cumulative intake was due to an increase in the number of meals for the lowest dose and in both the size and number of meals for the highest doses. With the same doses given at night the average increase in 12 hr intake was limited to 27% and was not dose-dependent. The changes in the various features of the meal pattern, observed under the effects of continuous insulin infusion, resembled those observed after VMH lesions. The similarities between these effects can be considered to support the assumption of the role played by hyperinsulinism in hypothalamic hyperphagia.

Dual effects of 2-deoxy-D-glucose on food intake in the rat: Inhibition at night and stimulation in the day-time

The effect of 2-deoxy-D-glucose on food intake in rats has been reexamined. The effects were compared following administration of 2-DG IP (250, 500, 750 mg/kg and saline) either at the beginning of a 12-hr dark or 12-hr light period. Ad lib food intake was recorded during the subsequent 24 hours. In the day-time 2-DG enhanced food intake. The increase was not dose-dependent. It was apparent only during the first four hours and was compensated during the following eight hours. At night, an inhibition in food intake was observed. This inhibition was mainly manifested during the first four hours and was not dose-dependent. However, a dose related compensation during the subsequent hours resulted in a dose-dependent inhibition of the nocturnal intake. A second expermient indicated that after an overnight fast 2-DG also inhibited the high food intake induced in the day-time. In a third experiment, insulin 10 IV SC combined to 2-DG was shown to further increase food intake in the day-time. At night the combined administration of insulin and 2-DG cancelled their respective opposite effects and no change of food consumption was observed. The results are interpreted in terms of the contrasted neuroendocrine and metabolic patterns prevailing in the two parts of the diurnal cycle.

The role of olfactory and orosensory factors in the alcohol preference of inbred strains of mice.

Abstract Removal of the olfactory bulbs eliminated the aversion to alcohol which is seen in normal BALB/c mice but did not abolish the preference for alcohol seen in normal C57BL mice. This result, along with the fact that BALB/c mice appear to avoid alcohol immediately, without prior experience, led to the hypothesis that BALB/c mice are more responsive than are C57BL mice to alcohol as a sensory stimulus. To test this hypothesis, a conditioning procedure was used in which normal animals of both strains drank alcohol in a single bottle test and were then injected with toxic lithium chloride. It was found that BALB/c mice learned aversions to alcohol, saccharin, and sucrose, whereas C57BL mice learned aversions to saccharin and sucrose but were deficient in learning an alcohol aversion. It was concluded that BALB/c mice normally avoid alcohol because of its odor but that for C57BL mice, other sensory cues or post-ingestional factors play an important role in their preference for alcohol.

Food related intravenous insulin self-administration in normal and diabetic rats

Abstract A chronic cardiac catheter was used to provide evidence for the ability of rats to perform intravenous insulin self-administrations. All rats tested rapidly learned to press a lever delivering a solution of regular insulin. The insulin self-injection, lasting several weeks, indicated a pattern specific to this hormone which differed from that of saline self-administration. On the average the daily amount of self-injected insulin was fivefold that of saline. Ninety percent of the daily insulin intake (versus 50% of the saline) were periprandially injected at the time of the meal and particularly just after the meal. The periprandial self-injected insulin positively correlated with the meal size. Fasted rats exhibited an immediate drop in the amount of the self-administered insulin. Upon discontinuation of the insulin delivery, the rats continued to press the inoperant lever with the same previously established meal-related pattern. Under insulin self-administration, the daily food and water intake did not increase and the body weight gain was not different from that of controls. In diabetic rats, previously trained on insulin self-injection, the transitory increase in the daily insulin intake was observed which later stabilized to a level lower than the pre-diabetic one. Results are discussed in relation to the reinforcing property of insulin and to neuroendocrine mechanism of food intake.

ACTH self-administration in rats.

The ability of rats to learn a lever pressing response reinforced by a contingent intravenous delivery of ACTH 1--24 and 4--10, was investigated. About 60% of the rats tested learned to press the lever for the two analogues that were infused at a rate of 2.08 microgram per second via a chronically implanted intrajugular catheter. Most of the animals exhibited sustained daily self-injections of 250 to 375 microgram of ACTH 1--24 and more variable amounts of ACTH 4--10. Comparisons with the self-administration of saline and altered responses following a change in the concentration of ACTH 1--24 solution indicated a positively reinforcing effect for the neuropeptide. The self-administration of the ACTH 4--10 analogue demonstrates that this reinforcing property of ACTH is not due to its adrenal stimulating activity. Brain targets possibly involved in the self-administration of ACTH are discussed.

Ethanol-induced taste aversion in ethanol-dependent and normal rats

It has previously been shown that the intragastric and parenteral administration of an acutely intoxicating dose of ethanol to naive rats paired with the oral intake of a flavored solution induces a conditioned taste aversion to the solution. Experiments have been designed to examine possible differences in the ethanol-induced aversion between naive rats and rats rendered ethanol dependent by chronic forced administration of alcohol. The classical conditioned taste aversion paradigm was used. Control rats and rats previously fed on an ethanol-containing liquid diet for 15 days were offered a saccharin solution for a 30-min period, 2 hr after the removal of either the control or the intoxicating liquid diet. In four groups of animals, the free intake of the flavored solution was immediately followed by either no injection or an ip administration of 1.5, 3.0 or 4.5 g/kg 20% ethanol solution. Three days later, the acquired aversion was tested with a second 30-min presentation of the saccharin solution. It was shown that in dependent rats, compared to controls, a single association between the oral intake and the withdrawal illness establishes a strong aversion to the flavored solution. In controls, aversion was induced by the three postingestive doses of ethanol. In intoxicated rats, 1.5 g/kg resulted in a maintained or slightly enhanced saccharin intake, whereas higher doses again induced the aversion. Nevertheless, the aversion obtained with the 3 g/kg was significantly lower than in controls. The findings of a withdrawal illness-induced aversion and of a maintained intake of this same solution, induced by the postingestional effect of a small dose of ethanol in dependent rats, are discussed in relation to the problem of the experimental establishment of behavioral ethanol dependence in rats.

Non-specific enhancement of ethanol-induced taste aversion by naloxone.

The conditioned taste aversion paradigm (CTA) was used to examine the effects of naloxone on ethanol-induced aversion towards a saccharine solution (3 conditioning and 11 extinction trials). Six groups of rats received conditioning trials consisting of two IP injections after saccharine presentation of different combinations of either ethanol (E: 1.75 g/kg), LiCl (L: 12 mEq/kg, 0.1 M), naloxone (N: 10 mg/kg) or saline (S); S-S, S-N, E-S, E-N, L-S and L-N. Naloxone by itself produced no aversion to the saccharin flavor. Based on the onset and extinction of aversion, naloxone significantly enhanced ethanol but also LiCl-induced CTA. The comparative data argues in favor of different mechanisms of action (1) between the aversive central effects of ethanol and morphine and (2) between ethanols acute behavioral effects and negatively reinforcing properties. Enhancement of ethanol and LiCl-induced CTA by naloxone is compatible with hypernociceptive action of the opiate-antagonist and with the pain-modulating role of opiates in the CNS.

Hypothalamic modulation of energy expenditure

The acute effects of electrical stimulation of the hypothalamus on energy expenditure as measured by indirect calorimetry were investigated in 20 unanaesthetized rats. Thirty sec of stimulation increased both O2 consumption and respiratory quotient (R.Q.). The largest magnitude hypermetabolic response (39% mean peak increase in O2 consumption) was produced by stimulation of the ventromedial hypothalamic nucleus. Stimulation of the lateral hypothalamus produced hypermetabolic effects similar to but smaller than those produced by medial stimulation. A number of considerations suggest that the hypermetabolism is not secondary to changes in motor activity, carbohydrate utilization or blood glucose levels. Consequently, these data suggest that the hypothalamus modulates energy expenditure through changes in non-shivering thermogenesis. These metabolic changes may modulate the effects of various hypothalamic manipulations on body weight.