Risperidone treatment increases CB1 receptor binding in rat brain

TY - JOUR

T1 - Risperidone treatment increases CB1 receptor binding in rat brain

AU - Secher, Anna

AU - Husum, Henriette

AU - Holst, Birgitte

AU - Egerod, Kristoffer Lihme

AU - Mellerup, Erling

N1 - Keywords: Adiponectin; Animals; Antipsychotic Agents; Brain; Cyclohexanols; Dopamine Antagonists; Eating; Ghrelin; Male; Motor Activity; Neuropeptide Y; Pro-Opiomelanocortin; Prolactin; Protein Binding; RNA, Messenger; Raclopride; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine D2; Receptors, Ghrelin; Risperidone; Tritium; Weight Gain

PY - 2010/3

Y1 - 2010/3

N2 - Background/Aims: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB1), the serotonin receptor 2C, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. Methods: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20% hydroxypropyl β-cyclodextrin) for 28 days. Expression of the aforementioned factors were examined together with plasma prolactin and ghrelin levels. Results: No difference in body weight gained during treatment was observed between risperidone and vehicle treated rats, but plasma risperidone levels positively correlated with visceral fat mass. Risperidone treatment increased CB1 receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB1 receptor mRNA. Risperidone treatment increased adiponectin mRNA. Conclusion: The present study showed that risperidone treatment altered CB 1 receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB 1 receptor density in brain regions involved in appetite and regulation of metabolic function.

AB - Background/Aims: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB1), the serotonin receptor 2C, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. Methods: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20% hydroxypropyl β-cyclodextrin) for 28 days. Expression of the aforementioned factors were examined together with plasma prolactin and ghrelin levels. Results: No difference in body weight gained during treatment was observed between risperidone and vehicle treated rats, but plasma risperidone levels positively correlated with visceral fat mass. Risperidone treatment increased CB1 receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB1 receptor mRNA. Risperidone treatment increased adiponectin mRNA. Conclusion: The present study showed that risperidone treatment altered CB 1 receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB 1 receptor density in brain regions involved in appetite and regulation of metabolic function.

U2 - 10.1159/000245220

DO - 10.1159/000245220

M3 - Journal article

C2 - 19815998

SN - 0028-3835

VL - 91

SP - 155

EP - 168

JO - Neuroendocrinology

JF - Neuroendocrinology

IS - 2

ER -