Consumption of palatable food decreases the anorectic effects of serotonergic, but not dopaminergic drugs in baboons

Abstract

We examined the effects of periodic access to a palatable, high sugar content food (candy) in 8 male baboons on the anorectic response to d-amphetamine, which increases dopamine, and dexfenfluramine, which increases serotonin. During candy access, up to 200 candies containing 75% of energy as sugar were available during the morning on Mondays, Wednesdays and Fridays; food pellets (19% of energy as sugar) were available in the afternoon and throughout the remaining days of the week. During candy access, baboons consumed a mean of 177 pieces of candy containing 696 kcal (2.91 MJ) in the morning compared to 44 food pellets and 150 kcal (0.63 MJ) in the morning on non-candy days. Food pellet intake was lower during candy access. Complete dose-response functions for the effects of the drugs on food pellet intake on days that candy was not available were determined before, during, and after the period of access to candy. Dexfenfluramine and amphetamine produced dose-dependent decreases in food pellet intake and increases in latency to eat food pellets before, during, and after candy access. During access to candy, the dose-response function for dexfenfluramine was shifted to the right indicating the development of tolerance, while that for amphetamine was shifted to the left indicating sensitization. Only the dose-response function for dexfenfluramine returned to baseline after candy access suggesting that the difference was specific to concurrent palatable food consumption. We hypothesize that tolerance to the effects of dexfenfluramine reflects a decrease in the satiating effect of serotonin release due to repeatedly eating large amounts of palatable food.

Diet-induced obesity and diet-resistant rats: differences in the rewarding and anorectic effects of d-amphetamine

“…Since previous studies have shown a lack of interaction between the anorectic properties of amphetamine and diet palatability / energy density (Wellman et al 1982), we hypothesize that the long-term exposure to the high-fat diet may have induced neuroadaptations in the dopaminergic system, which were responsible for the sensitized anorectic effect to D-amphetamine observed here. In support of this hypothesis are previous reports that repeated access to candies in baboons increases their sensitivity to the effects of D-amphetamine on the intake of both candies and regular food (Foltin 2011). …”

Neonatal serotonin reuptake inhibition reduces hypercaloric diet effects on fat mass and hypothalamic gene expression in adult rats

“…The increased expression of the 5‐HT 2C receptors after a hypercaloric diet is noteworthy because in our experimental model this type of diet produced different effects from those described in the literature. Classically, hypercaloric diets increase the proliferation of hypothalamic neurons that produce orexigenic peptides (Bouret et al, 2008) and reduce the anorexigenic effects of serotonergic drugs (Foltin, 2011). Moreover, diets rich in sugars and lipids can alter hypothalamic homeostatic control, increasing hunger signals and blocking satiety signals (Erlanson‐Albertsson, 2005).…”

The behavioral pharmacology of anorexigenic drugs in nonhuman primates

“…We examined the effects of consumption of a high-sucrose food on the anorexigenic actions of amphetamine, dexfenfluramine, heroin, and naloxone by determining complete dose–response functions before, during, and after a period of access to Skittles candy in eight experimentally-naive male baboons (Foltin, 2011). Baboons were administered with a test dose of drug or placebo on Tuesday and Thursday of each week.…”

“…This finding parallels the work of Morgan et al (2002) according to which submissive male cynomolgus monkeys self-administered more intravenous cocaine compared with dominant monkeys. On the basis of these findings, we examined the effect of social status (assigned by three independent observers) on Skittle consumption and response to pharmacological agents in the group of eight male baboons that were studied in the investigation by Foltin (2011). Although not significantly different, the four submissive male baboons consumed on average 18% more candy than the four dominant baboons.…”

“…Adapted with permission from Foltin, 2011: to increase clarity some original data points have been omitted. Data were obtained before, during, and after a period of access to candy.…”