Differential effects of methamphetamine on expression of neuropeptide Y mRNA in hypothalamus and on serum leptin and ghrelin concentrations in ad libitum-fed and schedule-fed rats

Mar 23, 2005Neuroscience

Methamphetamine's different effects on brain hunger signals and blood appetite hormones in freely eating versus scheduled-feeding rats

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Abstract

Administration of methamphetamine (7.5 mg/kg) significantly inhibited food intake in scheduled feeding conditions while altering neuropeptide expression and metabolic hormone levels.

Methamphetamine reduced neuropeptide Y (NPY) mRNA expression in the hypothalamus of scheduled feeding animals, which may contribute to its appetite-suppressing effects.
In scheduled feeding conditions, methamphetamine did not affect expression of agouti-related peptide (AgRP) mRNA or serum concentrations of leptin, insulin, or ghrelin.
In ad libitum animals, methamphetamine increased NPY mRNA expression and decreased serum leptin and insulin levels while increasing serum ghrelin concentrations.
Elevated NPY expression in ad libitum conditions may be linked to the observed decreases in leptin and insulin and increases in ghrelin secretion.

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Relatively little is known concerning the interaction of psychostimulants with hypothalamic neuropeptide systems or metabolic hormones implicated in regulation of energy balance. The present studies tested whether methamphetamine alters the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP), two important orexigenic neuropeptides, or proopiomelanocortin (POMC), the precursor for the anorexigenic peptide alpha-melanocyte-stimulating hormone, or the secretion of leptin, insulin and ghrelin, concomitant with inhibition of food intake. Female rats were either fed ad libitum (AL) or placed on a scheduled feeding (SF) regimen, with access to food limited to 4 h/day. Administration of (+/-)-methamphetamine (7.5 mg/kg, i.p.) 2 h prior to food presentation significantly inhibited food intake in SF animals, but did not affect intake in AL animals. In a separate study, AL and SF animals were killed just prior to expected food presentation, and expression of NPY, AgRP and POMC mRNAs in hypothalamus was determined using in situ hybridisation; concentrations of leptin, insulin and ghrelin in serum were determined with radioimmunoassays. In saline-treated, SF controls, NPY and AgRP mRNA expression in arcuate nucleus and serum ghrelin were significantly elevated, and serum leptin and insulin were significantly reduced. Methamphetamine reversed the up-regulation of NPY mRNA expression observed in the SF condition, without affecting AgRP mRNA or the serum concentrations of metabolic hormones. However, in AL animals, NPY mRNA expression in arcuate and dorsomedial nuclei was significantly increased by methamphetamine, which also reduced serum leptin and insulin and increased serum ghrelin concentrations. These findings suggest that the inhibition of NPY expression in SF animals may be a mechanism underlying the anorexigenic effect of methamphetamine seen in this condition. The increase in NPY expression produced by methamphetamine in AL animals may be mediated by the ability of this drug to decrease secretion of leptin and insulin and increase secretion of ghrelin.

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Differential effects of methamphetamine on expression of neuropeptide Y mRNA in hypothalamus and on serum leptin and ghrelin concentrations in ad libitum-fed and schedule-fed rats

Abstract

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