TY - JOUR
T1 - Olanzapine and sibutramine have opposing effects on the motivation for palatable food
AU - van der Zwaal, Esther M.
AU - Janhunen, Sanna K.
AU - Luijendijk, Mieneke C. M.
AU - Baclesanu, Roxana
AU - Vanderschuren, Louk J. M. J.
AU - Adan, Roger A. H.
AU - la Fleur, Susanne E.
PY - 2012
Y1 - 2012
N2 - Both olanzapine and sibutramine target serotonergic and noradrenergic neurotransmission and influence body weight, but in opposite ways. The second-generation antipsychotic olanzapine, an antagonist at serotonergic and noradrenergic receptors, frequently induces weight gain as a side-effect, whereas sibutramine, a noradrenaline/serotonin reuptake inhibitor, is known as a weight-reducing agent. To investigate whether altered motivation for palatable food influences the effect of these drugs on body weight, we determined their effects on responding for sucrose pellets under a progressive ratio schedule of reinforcement in rats. We found that a low dose of olanzapine selectively increased responding to sucrose, without affecting free-feeding intake of sucrose. In contrast, sibutramine dose-dependently reduced responding to sucrose and similarly reduced free-feeding intake. Furthermore, coadministration of a dose of sibutramine that failed to affect responding to sucrose when administered alone prevented the increase in motivation by the effective dose of olanzapine. These data show that increased motivation for palatable food is likely to be a significant contributor to olanzapine-induced weight gain. Moreover, the ability of sibutramine to reduce this motivation for palatable food may play an important role in the efficacy of sibutramine as an add-on treatment to counteract olanzapine-induced weight gain. Behavioural Pharmacology 23:198-204 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
AB - Both olanzapine and sibutramine target serotonergic and noradrenergic neurotransmission and influence body weight, but in opposite ways. The second-generation antipsychotic olanzapine, an antagonist at serotonergic and noradrenergic receptors, frequently induces weight gain as a side-effect, whereas sibutramine, a noradrenaline/serotonin reuptake inhibitor, is known as a weight-reducing agent. To investigate whether altered motivation for palatable food influences the effect of these drugs on body weight, we determined their effects on responding for sucrose pellets under a progressive ratio schedule of reinforcement in rats. We found that a low dose of olanzapine selectively increased responding to sucrose, without affecting free-feeding intake of sucrose. In contrast, sibutramine dose-dependently reduced responding to sucrose and similarly reduced free-feeding intake. Furthermore, coadministration of a dose of sibutramine that failed to affect responding to sucrose when administered alone prevented the increase in motivation by the effective dose of olanzapine. These data show that increased motivation for palatable food is likely to be a significant contributor to olanzapine-induced weight gain. Moreover, the ability of sibutramine to reduce this motivation for palatable food may play an important role in the efficacy of sibutramine as an add-on treatment to counteract olanzapine-induced weight gain. Behavioural Pharmacology 23:198-204 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
U2 - https://doi.org/10.1097/FBP.0b013e3283512ca1
DO - https://doi.org/10.1097/FBP.0b013e3283512ca1
M3 - Article
C2 - 22327018
SN - 0955-8810
VL - 23
SP - 198
EP - 204
JO - Behavioural pharmacology
JF - Behavioural pharmacology
IS - 2
ER -