Involvement of hypothalamic neuropeptide Y in regulating the amphetamine-induced appetite suppression in streptozotocin diabetic rats.
ABSTRACT 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.
- Brain Research 02/1975; 84(1):160-7. · 2.88 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Untreated streptozocin-induced diabetic (STZ-D) rats have previously been shown to have significantly increased hypothalamic concentrations of neuropeptide Y (NPY), a regulatory peptide that powerfully stimulates eating and drinking and inhibits secretion of several pituitary hormones when injected centrally. Tissue NPY concentrations have been measured by radioimmunoassay in selected hypothalamic regions microdissected from fresh, unfixed brain slices to localize diabetes-associated NPY changes precisely within the hypothalamus. Significant (35-200%) increases in NPY concentrations (P less than .01 vs. matched nondiabetic controls) were found in specific hypothalamic regions between 3 and 14 wk after induction of STZ-D. These regions included the paraventricular and ventromedial nuclei and lateral hypothalamic area, major appetite-regulating areas that are sensitive to the hyperphagic and polydipsic actions of NPY. Increased NPYergic activity in these areas may, at least partly, drive the increased eating and drinking characteristic of STZ-D. NPY concentrations were also increased in the arcuate nucleus and medial preoptic area. Because both of these regions are important in modulating pituitary hormone secretion, local NPY increases may be involved in the impaired secretion of luteinizing hormone, thyroid-stimulating hormone, growth hormone, and prolactin known to occur in STZ-D. Our finding of NPY increases in specific hypothalamic nuclei associated with functional changes found in STZ-D suggests that this peptide may have a role in the altered metabolic and neuroendocrine regulation of the syndrome.Diabetes 04/1989; 38(3):321-7. · 7.90 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Tolerance to amphetamine-induced hypophagia is lost when drug injections are withdrawn for 4 weeks while milk tests are continued (Wolgin and Hughes 1996). The purpose of this study was to determine whether the loss of tolerance is a function of drug withdrawal per se. Rats made tolerant to amphetamine (2 mg/kg, IP) were assigned to one of three groups. During the next 4 weeks (phase), one group continued to receive amphetamine injections prior to daily milk tests (Before group), one group received drug injections after the milk tests (After group), and one group received injections of saline prior to the milk tests (Saline group). Dose-response tests revealed that the Before group retained tolerance, whereas the After and Saline groups lost tolerance. When retested with chronic injections of amphetamine prior to milk, the After and Saline groups reacquired tolerance more rapidly, and to a greater extent, than non-tolerant controls. These results demonstrate that the loss of tolerance is not due to drug withdrawal per se, but may be due to the unlearning of behavioral strategies previously acquired under the drug.Psychopharmacology 09/1997; 132(4):342-9. · 4.06 Impact Factor