Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y

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Abstract
NEUROPEPTIDE Y (NPY), a 36-amino-acid transmitter distributed throughout the nervous system1,2, is thought to function as a central stimulator of feeding behaviour1–4. NPY has also been implicated in the modulation of mood5, cerebrocortical excitability6, hypothalamic–pituitary signalling7, cardiovascular physiology1,8 and sympathetic function9,10. However, the biological significance of NPY has been difficult to establish owing to a lack of pharmacological antagonists. We report here that mice deficient for NPY have normal food intake and body weight, and become hyperphagic following food deprivation. Mutant mice decrease their food intake and lose weight, initially to a greater extent than controls, when treated with recombinant leptin. Occasional, mild seizures occur in NPY-deficient mice and mutants are more susceptible to seizures induced by a GABA (γ-aminobutyric acid) antagonist. These results indicate that NPY is not essential for certain feeding responses or leptin actions but is an important modulator of excitability in the central nervous system.