Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats

Miyuki Ota, Keiji Mori, Akira Nakashima, Yoko S. Kaneko, Kentaro Fujiwara, Mitsuyasu Itoh, Akio Nagasaka, Akira Ota

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

1. Risperidone is an atypical antipsychotic drug that possesses 5-hydroxytryptamine 5-HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism. 2. Excessive bodyweight gain is one of the side-effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone-induced bodyweight change in rats by examining the expression of leptin, an appetite-regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)-1, a substance promoting energy expenditure in the brown adipose tissues (BAT). 3. Eight-week-old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and β3-adrenoceptor(β3-AR) genes in WAT and BAT were quantified using real-time polymerase chain reaction amplification. 4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and β3-AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone. 5. Although the changes in food intake observed in risperidone-injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP-1 mRNA expression level in BAT. The role of leptin in risperidone-induced alterations in bodyweight gain remain to be clarified.

Original languageEnglish
Pages (from-to)980-989
Number of pages10
JournalClinical and Experimental Pharmacology and Physiology
Volume29
Issue number11
DOIs
Publication statusPublished - 29-10-2002

Fingerprint

Risperidone
Antipsychotic Agents
Leptin
White Adipose Tissue
Injections
Brown Adipose Tissue
Eating
Prolactin
Gene Expression
Serum
Adrenergic Receptors
Energy Metabolism
Ghrelin
Dopamine D2 Receptors
Haloperidol
Real-Time Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Ota, Miyuki ; Mori, Keiji ; Nakashima, Akira ; Kaneko, Yoko S. ; Fujiwara, Kentaro ; Itoh, Mitsuyasu ; Nagasaka, Akio ; Ota, Akira. / Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats. In: Clinical and Experimental Pharmacology and Physiology. 2002 ; Vol. 29, No. 11. pp. 980-989.
@article{392b86fc27c7428ca1005507ee01d5dc,
title = "Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats",
abstract = "1. Risperidone is an atypical antipsychotic drug that possesses 5-hydroxytryptamine 5-HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism. 2. Excessive bodyweight gain is one of the side-effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone-induced bodyweight change in rats by examining the expression of leptin, an appetite-regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)-1, a substance promoting energy expenditure in the brown adipose tissues (BAT). 3. Eight-week-old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and β3-adrenoceptor(β3-AR) genes in WAT and BAT were quantified using real-time polymerase chain reaction amplification. 4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and β3-AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone. 5. Although the changes in food intake observed in risperidone-injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP-1 mRNA expression level in BAT. The role of leptin in risperidone-induced alterations in bodyweight gain remain to be clarified.",
author = "Miyuki Ota and Keiji Mori and Akira Nakashima and Kaneko, {Yoko S.} and Kentaro Fujiwara and Mitsuyasu Itoh and Akio Nagasaka and Akira Ota",
year = "2002",
month = "10",
day = "29",
doi = "10.1046/j.1440-1681.2002.t01-1-03755.x",
language = "English",
volume = "29",
pages = "980--989",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "11",

}

Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats. / Ota, Miyuki; Mori, Keiji; Nakashima, Akira; Kaneko, Yoko S.; Fujiwara, Kentaro; Itoh, Mitsuyasu; Nagasaka, Akio; Ota, Akira.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 29, No. 11, 29.10.2002, p. 980-989.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats

AU - Ota, Miyuki

AU - Mori, Keiji

AU - Nakashima, Akira

AU - Kaneko, Yoko S.

AU - Fujiwara, Kentaro

AU - Itoh, Mitsuyasu

AU - Nagasaka, Akio

AU - Ota, Akira

PY - 2002/10/29

Y1 - 2002/10/29

N2 - 1. Risperidone is an atypical antipsychotic drug that possesses 5-hydroxytryptamine 5-HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism. 2. Excessive bodyweight gain is one of the side-effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone-induced bodyweight change in rats by examining the expression of leptin, an appetite-regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)-1, a substance promoting energy expenditure in the brown adipose tissues (BAT). 3. Eight-week-old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and β3-adrenoceptor(β3-AR) genes in WAT and BAT were quantified using real-time polymerase chain reaction amplification. 4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and β3-AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone. 5. Although the changes in food intake observed in risperidone-injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP-1 mRNA expression level in BAT. The role of leptin in risperidone-induced alterations in bodyweight gain remain to be clarified.

AB - 1. Risperidone is an atypical antipsychotic drug that possesses 5-hydroxytryptamine 5-HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism. 2. Excessive bodyweight gain is one of the side-effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone-induced bodyweight change in rats by examining the expression of leptin, an appetite-regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)-1, a substance promoting energy expenditure in the brown adipose tissues (BAT). 3. Eight-week-old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and β3-adrenoceptor(β3-AR) genes in WAT and BAT were quantified using real-time polymerase chain reaction amplification. 4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and β3-AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone. 5. Although the changes in food intake observed in risperidone-injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP-1 mRNA expression level in BAT. The role of leptin in risperidone-induced alterations in bodyweight gain remain to be clarified.

UR - http://www.scopus.com/inward/record.url?scp=0036400604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036400604&partnerID=8YFLogxK

U2 - 10.1046/j.1440-1681.2002.t01-1-03755.x

DO - 10.1046/j.1440-1681.2002.t01-1-03755.x

M3 - Article

VL - 29

SP - 980

EP - 989

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 11

ER -