Involvement of hypothalamic neuropeptide Y in regulating the amphetamine-induced appetite suppression in streptozotocin diabetic rats.
OBJECTIVE
Amphetamine (AMPH) is a well-known anorectic agent. In normal rats, AMPH-induced anorexia has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. In diabetic rats, however, if this anorectic response of AMPH might still be observed was uncertain.


METHODS
Rats (including normal, diabetic and insulin-treated diabetic rats) were given daily with saline or AMPH for 6 days. Changes in food intake, plasma glucose level (PGL) and NPY content of these rats were measured and compared.


RESULTS
The AMPH-induced anorectic response was altered in diabetic rats. Although the anorectic effects of AMPH on the first day of dosing were similar between diabetic and control rats, diabetic rats developed tolerance to this anorexia more rapidly than control rats. This alteration was independent of PGL since PGL levels were not changed following AMPH treatment and PGL normalization induced by phlorizin could not restore the level of AMPH anorexia. On the other hand, this alteration was dependent on the action of NPY because NPY contents were decreased following AMPH treatment and the replacement of insulin in diabetic rats could restore both NPY content and AMPH anorexia.


CONCLUSIONS
These results suggested that the elevated hypothalamic NPY content in diabetic rats was involved in modifying the anorectic response of AMPH.
Kuo
Dong-Yih
DY
Department of Physiology, Chung Shan Medical University, Taichung 40201, Taiwan, ROC. dykuo@csmu.edu.tw
D000662:Amphetamines / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000378:metabolism* / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000662:Amphetamines; D001067:Appetite Depressants; D001786:Blood Glucose; D007328:Insulin; D009478:Neuropeptide Y