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Aim:The lateral hypothalamus (LH) is known as the hunger center, but the mechanisms through which the LH regulates food intake are unclear. Since GABA neurons are reported to project to the LH, the present study investigated the role of GABAergic function in the LH in the regulation of feeding behavior.Methods: GABA levels in the LH were measured by in vivo microdialysis. Food intake after drug injection into the LH was measured every 1 hour for 4 hours. The mRNA levels were measured using RT-PCR.Results: Food intake significantly increased GABA levels in the LH, suggesting that food intake stimulates GABAergic function in the LH. Injection of the GABA A receptor agonist muscimol into the LH significantly inhibited food intake, whereas injection of the GABA A receptor antagonist bicuculline into the LH did not significantly affect food intake. The inhibitory effect of muscimol injected into the LH was blocked by co-administration of bicuculline. These results indicate that the stimulation of GABA A receptors in the LH inhibits food intake. We next examined whether the stimulation of GABA A receptors affects hypothalamic neuropeptides that are known to regulate feeding behavior. The injection of muscimol significantly decreased preproorexin mRNA in the hypothalamus.

Background and Purpose: Patients with diabetes mellitus are reported to show a raised prevalence of mental disorders, which may be reflected in impaired social interaction. However, the mechanisms underlying such impairment in diabetes are unknown.Experimental Approach: The present study investigated whether social interaction is impaired in diabetic mice and whether central neuropeptide Y (NPY) and glutamatergic function are involved in such impairment.Key Results: In the three-chamber test, social novelty preference, but not sociability, was impaired in streptozotocin (STZ)-induced diabetic mice. The mRNA level of NPY in the hypothalamus was increased in STZ-induced diabetic mice. Injection of the NPY Y 2 receptor agonist NPY 13-36 into naïve mice impaired social novelty preference, but not sociability, and this effect was inhibited by the Y 2 receptor antagonist BIIE 0246. BIIE 0246 also reversed the impairment of social novelty preference in STZ-induced diabetic mice. Similarly, injection of the AMPA receptor agonist AMPA into naïve mice impaired social novelty preference, but not sociability, and this effect was inhibited by the AMPA receptor antagonist NBQX. Impairment of social novelty preference induced by NPY 13-36 was inhibited by NBQX, whereas impairment of social novelty preference induced by AMPA was not inhibited by BIIE 0246. Finally, impairment of social novelty preference in STZ-induced diabetic mice was reversed by NBQX. Conclusion and Implications:These findings suggest that NPY neurons are activated in diabetic mice and that this may impair social novelty preference by promoting glutamatergic function through Y 2 receptors.

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