Marc Fantino

Mesolimbic dopaminergic system activity as a function of food reward: A microdialysis study

The mesolimbic dopaminergic system (MDS) has been shown to be implicated in feeding behaviors. The present experiment was conducted to examine the effects of the sensory properties of food ingested on MDS activity. Microdialysis coupled to high-performance liquid chromatography with electrochemical detection was employed to measure the extracellular levels of dopamine (DA) and its main metabolites (DOPAC and HVA) in the nucleus accumbens of freely moving rats. During microdialysis sessions rats had access or not to powdered foods varying in palatability: short cakes as highly palatable (HP) food and regular chow as low palatable (LP) food. In the absence of food, there were no alterations in extracellular levels of DA, DOPAC, and HVA. During feeding, DA rose significantly with a greater rise for the HP than the LP food. Levels of DOPAC and HVA only reached significance with the HP food. The results indicate that the MDS is activated on ingestion of food, and suggest that MDS activity is related to the rewarding properties of foods.

Influence of repeated consumption of beverages containing sucrose or intense sweeteners on food intake

Objective: To investigate the influence of ingestion of beverages with sucrose or with intense sweeteners on food intake (FI) and on hunger ratings in before and after a month of daily consumption of beverages.Design: Experimental study.Setting: Department of Physiology, University Hospital, Dijon, France.Subjects: In all, 12 men and 12 women, aged 20–25 y.Interventions: Four beverages contained either sucrose (E+:100 g/l, 1672 kJ) or intense sweeteners (E−: null energy content) and were flavoured with either orange (O) or raspberry (R). FI was measured in the lab during two 2-consecutive-day periods, carried out on 2 successive weeks (session 1). The subjects drank 2 l of either E+ or E− beverages on the first day of both weekly periods, according to a balanced randomised design. E+ was paired with O for 50% of subjects and with R for the other 50%. Subjects were then habituated over a 4-week period to both beverages, consuming 1 l of E+ beverage on odd days and 1 l of E– drink on even days. After this period, the measurements of session 1 were repeated (session 2, weeks 7–8). Finally, FI was measured for two more 2-day periods (weeks 9–10) after the association between flavour and energy content was reversed (session 3).Results: The E– drinks were less palatable than the E+ drinks. Besides, we observed that FI was not reduced in response to a liquid extra caloric load and there was no change in hunger ratings after the beverages in any of the sessions.Conclusion: Ingestion of caloric beverages induced a positive energy balance and the continuous exposure phase to these beverages over 1 month did not improve FI adaptation in response to the extra energy provided by the beverages.Sponsorship: This study was sponsored by SEV, Bourg la Reine, France; the French Ministère de la Recherche et de la Technologie (Programme AGROBIO-Aliments Demain) and the Regional Council of Burgundy (Dijon, France).

Origin of olfacto-gustatory alliesthesia: Intestinal sensitivity to carbohydrate concentration?

Gustatory and olfactory alliesthesia was observed in nine healthy adult humans who received on three different days an intragastric load of 50 g glucose dissolved into various amounts of water in order to make 100, 200 and 400 ml of solution. Maximal alliesthesia to sweet stimuli was observed with the smallest volume, i.e., highest concentration. Comparison of these results with previous results [7], obtained not by varying the volume but by varying the glucose mass, shows identity. Maximal alliesthesia to olfactory anchovy and ViandoxR was also observed after ingestion of the most concentrated gastric load. Maximal negative alliesthesia was observed about 45 min after the gastric load; thereafter alliesthesia tended to decrease. A gastric 200 ml load containing 40 g Mannitol, a nonabsorbed sugar, was followed by a strong negative alliesthesia to alimentary stimuli. Ten g glucose in 20 ml solution produced a more intense and rapid alliesthesia when injected into the duodenum than when injected into the stomach. It may be concluded that postinjective negative alliesthesia for alimentary stimuli can be caused by intraduodenal concentration of nutrients, probably sensed by duodenal nervous chemoreceptors.

Influence of the amount of food ingested on mesolimbic dopaminergic system activity : A microdialysis study

The mesolimbic dopaminergic system (MDS) has been shown to be activated by ingestive behaviors, and it has been suggested that this activation may be related to the rewarding properties of foods. Because rats eat more when given a more palatable diet, this study was undertaken to determine-the relationship between the amount of food ingested and DA release in the nucleus accumbens of freely moving rats. The extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured by high-performance liquid chromatography with electrochemical detection on microdialysis samples from the nucleus accumbens. Each rat underwent three microdialysis sessions that differed in feeding conditions: on the first day they had access to a highly palatable diet (short cakes) ad lib; on the second day they were given half the amount consumed on the previous day of the same food; and on the third day they were deprived of food. In the absence of food, there were no significant alterations in extracellular levels of DA, DOPAC, and HVA. During feeding, levels of DA and its two metabolites rose. DA release in the nucleus accumbens was related to the amount of food ingested. As the amount ingested is a component of the reinforcement associated with food intake, this result is consistent with a direct relationship between MDS activity and food reward.

Evidence for a direct central anorectic effect of tumor-necrosis-factor-alpha in the rat

This study was designed to investigate the effect of tumor necrosis factor-alpha (TNF) on the control of food intake in rat. The specific aims were: a) to evaluate the effects of central (ICV) or peripheral (IP) microdoses of TNF on food intake; b) to show that the TNF-induced anorexia results from a direct action of the mediator on the central nervous system; c) to demonstrate that the anorexic activity of TNF is not due to nonspecific malaise. In the first experiment, ICV administration (0.5-4.0 micrograms) of recombinant-murine tumor necrosis factor-alpha (rmTNF) significantly reduced food intake in a dose-dependent manner. The maximal effect (-66%) was observed 5 h after a 4.0 micrograms dose. In contrast, rm TNF did not affect feeding behavior when injected IP, indicating that the anorexic activity was centrally mediated. The estimated DE50 was 2.0 micrograms/rat by the ICV route. In the second experiment, the place conditioning paradigm was used to show that TNF administered ICV at 2.0 micrograms/rat did not induce aversive or deleterious effects as compared to naltrexone given IP at the equi-anorectic dose 5.0 mg/kg. It was concluded that TNF reduces food intake in rats by a direct action on the central nervous system.

Safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults.

In the present pilot study, intradermal ID delivery systems with a BD microneedle from 1 to 3mm in length, and epidermal delivery (BD skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. Circulating neutralizing antibodies were measured against the rabies virus after the Vero cells rabies vaccine was administered at D0, D7, D21 and D49. This clinical evaluation in 66 healthy volunteers shows that ID delivery using BD microneedle technology of 1/4 the IM antigen dose is safe, efficient and reliable, resulting in a protective seroconversion rate. In contrast, the epidermal delivery route did not produce an immune response against the rabies vaccine.

Consequence of Omitting or Adding a Meal in Man on Body Composition, Food Intake, and Metabolism

Objective: To investigate in man the consequence on body composition and related biological and metabolic parameters of omitting or adding a meal.

Body weight set-point changes during the ovarian cycle: Experimental study of rats using hoarding behavior

Body weight, food intake and food hoarding behavior were measured in 12 female rats fed ad lib and correlated with the ovarian cycle of each. All three parameters fluctuated synchronously, being minimal at estrus and maximal at diestrus. The hypothesis was then tested that these fluctuations result from cyclical oscillation of the body weight set-point entrained by the ovarian cycle, as previously proposed by others. The linear correlation between hoarding behavior and body weight was used to extrapolate the computed threshold of body weight at which hoarding behavior occurred at diestrus and at estrus; this threshold has already been shown to be a good index of the body weight set-point. The results indicated that the regression of hoarding behavior on body weight was virtually identical at estrus and diestrus (same slope), but the critical level of body weight for the onset of hoarding behavior was 31.2 g lower at estrus than at diestrus. This provides direct evidence in the rat of fluctuation of the body weight set-point with the ovarian cycle.

Comportement thermoregulateur chezRana esculenta

Summary1.Behavioural temperature regulation (seeking of a thermopreferendum) of frogs (Rana esculenta) has been studied in an aqueous thermal gradient during selective heating of the spinal cord.2.These experiments confirmed that the mean thermopreferendum in this species is about 26° C without spinal cord heating.3.After spinal heating frogs chose a colder ambient temperature. This decrease of the thermopreferendum was proportional to the heating power dissipated in the thermode.4.A similar behavior has been obtained after complete denervation of the dorsal skin. Therefore the change in thermopreferendum was triggered by deep thermal receptors.5.The measurement of colonic, cephalic, brain and spinal temperatures showed that only the spinal region was heated by the thermode. It is therefore reasonable to assume that the behaviour was triggered by spinal thermoreceptors.6.During spinal heating the spinal temperature does not surpass 35° C. Everything is as if the frog behaviour prevented internal temperature from surpassing 35°C.7.As in mammals and birds it is reasonable to assume the existence of a warm sensitivity in the spinal cord of ectothermes. This sensitivity gives rise to a thermoregulatory behaviour.

Negative allesthesia and decreased endogenous opiate system activity in anorexia nervosa

The combined effects of an intragastric load of glucose compared to water and of naltrexone compared to placebo were tested on preference for sucrose in six anorectic patients. While in normal subjects, glucose-induced negative allesthesia is known to disappear upon loss of weight, it persisted in anorexia nervosa (AN) despite a major weight loss; furthermore, in contrast with its effects in normoponderal subjects, naltrexone at the dose of 25 mg did not decrease the preference for sucrose nor did it enhance glucose-induced allesthesia. Basal plasma beta endorphin level determined by radioimmunoassay was higher in AN than in normal subjects (75 +/- 6.1 pmoles/l vs. 13 +/- 3.8 pmoles/l) (p less than 0.001). It is suggested that a decrease in endogenous system opiate activity might be associated with food refusal and body weight loss in anorexia nervosa.