Risperidone treatment increases CB1 receptor binding in rat brain.
OBJECTIVE
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 (CB(1)), 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 beta-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 CB(1) receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB(1) receptor mRNA. Risperidone treatment increased adiponectin mRNA.


CONCLUSIONS
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.
Secher
Anna
A
Laboratory of Neuropsychiatry, Rigshospitalet, Copenhagen, Denmark. anna.secher@rh.regionh.dk
Husum
Henriette
H
Holst
Birgitte
B
Egerod
Kristoffer Lihme
KL
Mellerup
Erling
E
D052242:Adiponectin / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003511:Cyclohexanols / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D054439:Ghrelin / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011388:Prolactin / Q000097:blood; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics; D018967:Risperidone / Q000097:blood / Q000494:pharmacology*; D014316:Tritium; D015430:Weight Gain / Q000187:drug effects*
D052242:Adiponectin; D014150:Antipsychotic Agents; D003511:Cyclohexanols; D018492:Dopamine Antagonists; D054439:Ghrelin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D054440:Receptors, Ghrelin; D014316:Tritium; D020891:Raclopride; D011333:Pro-Opiomelanocortin; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D011388:Prolactin; D018967:Risperidone