Involvement of hypothalamic neuropeptide Y in regulating the amphetamine-induced appetite suppression in streptozotocin diabetic rats

Department of Physiology, Chung Shan Medical University, Taichung 40201, Taiwan, ROC.
Regulatory Peptides (Impact Factor: 1.83). 05/2005; 127(1-3):19-26. DOI: 10.1016/j.regpep.2004.10.008
Source: PubMed


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.
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.
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.
These results suggested that the elevated hypothalamic NPY content in diabetic rats was involved in modifying the anorectic response of AMPH.

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    • "Several studies have extensively investigated the specific mechanisms that explain the amphetamine's anorexic action. These studies have demonstrated that the anorectic agent induced its effects through the cerebral release of dopamine, and the consequent activation of D1-like and D2-like receptors [9] [10] [11] [5], decreasing the level of hypothalamic NPY [12] [13]. Behavioral studies have reported that non-selective activation of dopamine D2 subtype receptors decreased food intake and the rate of eating [14]. "
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