Effects of sibutramine and rimonabant in rats trained to discriminate between 22- and 2-h food deprivation

Abstract

Objective The objective of the study was to evaluate whether sibutramine and rimonabant, drugs that decrease food intake in human and non-human animals, affect the discriminative stimulus effects associated with acute food deprivation ("hunger"). Materials and methods Rats were trained to discriminate between 22-and 2-h food deprivation in a two-lever choice procedure. After rats acquired the discrimination, subjects were food-restricted for 22 h and administered with sibutramine (0.32-10 mg/kg, p.o.) or rimonabant (0.32-10 mg/kg, s.c.) before a generalization test session. Results Sibutramine (3.2 mg/kg) produced significant decreases in 22-h deprivation-appropriate responding, response rates (resulting in lever pressing rates similar to those following 2-h food deprivation), and food intake measured 1 h after the generalization test. A larger sibutramine dose eliminated responding and significantly reduced food intake. Rimonabant did not alter the discriminative stimulus effects of 22-h food deprivation, but rimonabant did significantly reduce both response rates and food intake. Conclusion Sibutramine appears to decrease food intake by reducing hunger sensations associated with food deprivation. In contrast, rimonabant does not alter the discrimination of acute food deprivation. The use of food-deprivation discrimination techniques may be useful in identifying the role of specific neuroactive compounds in eating stimulated by a sense of hunger and may aid in medication development for more effective treatments for obesity and other eating-related conditions.

Effect of Oxytocin on Hunger Discrimination

“…Thus, CCK produced effects that resembled a lack of hunger. Similar outcomes to those induced by CCK were seen in response to an anti-obesity drug, sibutramine (27, 28).…”

“…As food preloads appropriately change animals' perception of the length of deprivation, the parallel effect of anorexigens given instead of a food preload, indicates that they reduce a feeling of hunger. This approach allowed to implicate CCK and sibutramine as agents that can aid in controlling hunger (and deemed rimonabant ineffective in this process) (26, 27). Of note is the fact that, in contrast to anorexigens, some orexigens (NPY or ghrelin) make animals perceive the short 2-h deprivation as the state of hunger (28, 40).…”

Addition of a low dose of rimonabant to orlistat therapy decreases weight gain and reduces adiposity in dietary obese rats

“…Very few drugs have been developed for the treatment of obesity and those that have been approved for use have limited success. Marked increases in the prevalence of obesity, in addition to the consequent health and economic burdens, heighten the need for new insights into the mechanisms of anti‐obesity medications …”

The rise (and fall?) of drug discrimination research

“…Rats have been trained to discriminate between food satiation and food deprivation by Jewett and colleagues. This approach has been used to examine various peptides and neurotransmitters involved in feeding and to identify drugs that potentially modify appetite (Jewett et al, 2009). An early review of drug discrimination suggested possible applications to a variety of other internally mediated events that could be studied in conjunction with drugs such as pain, inflammation, and hypertension (Lal, 1977).…”