A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain.
The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 microg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 microg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.
Moon
Bo-Hyun
BH
Department of Pharmacology and Division of Brain Korea 21, Biomedical Science, Korea University College of Medicine, 126-1, 5-ga, Anam-dong, Sungbuk-gu, Seoul 136-705, Republic of Korea.
Hong
Chang Gwun
CG
Kim
Soo-Young
SY
Kim
Hyun-Ju
HJ
Shin
Seung Keon
SK
Kang
Seungwoo
S
Lee
Kuem-Ju
KJ
Kim
Yong-Ku
YK
Lee
Min-Soo
MS
Shin
Kyung-Ho
KH
D000818:Animals; D001127:Arginine Vasopressin / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011333:Pro-Opiomelanocortin / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone