Dopaminergic mechanisms in the lateral hypothalamus regulate feeding behavior in association with neuropeptides.

This study investigated dopaminergic function in the lateral hypothalamus (LH) in the regulation of feeding behavior. Refeeding increased dopamine levels in the LH. Glucose injection also increased dopamine levels in the LH. When the retrograde tracer Fluoro-Gold (FG) was injected into the LH, FG-positive cells were found in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNC), which were mostly tyrosine hydroxylase-positive. Injection of the dopamine D1 receptor agonist SKF 38393, but not the antagonist SCH 23390, into the LH increased food intake. Similarly, injection of the dopamine D2 receptor agonist quinpirole, but not the antagonist l-sulpiride, into the LH increased food intake. The effect of each agonist was blocked by its respective antagonist. Furthermore, injection of quinpirole, but not SKF 38393, decreased the mRNA level of preproorexin. In addition, injection of SKF 38393 decreased the mRNA levels of neuropeptide Y and agouti-related peptide, whereas the injection of quinpirole increased the mRNA level of proopiomelanocortin. These results indicate that food intake activates dopamine neurons projecting from the VTA/SNC to the LH through an increase in blood glucose levels, which terminates food intake by stimulation of dopamine D1 and D2 receptors. It is also possible that stimulation of dopamine D1 and D2 receptors in the LH inhibits feeding behavior through different neuropeptides.

Neuropeptide Y and glutamatergic mechanisms in the amygdala and ventral hippocampus differentially mediate impaired social behavior in diabetic mice.

Though patients with diabetes mellitus are reported to show deficits in social interaction, the mechanisms of these impairments are unclear. The present study investigated the role of AMPA and neuropeptide Y (NPY) receptors in the ventral hippocampus (vHC) and basolateral amygdala (BLA) in the social behavior of diabetic mice. In the three-chamber test, streptozotocin (STZ)-induced diabetic mice showed impairment in social novelty preference, but not in sociability. Injection of the AMPA receptor antagonist NBQX into vHC or BLA each restored social novelty preference in STZ-induced diabetic mice. NPY content in amygdala, but not in vHC, of STZ-induced diabetic mice was increased relative to non-diabetic mice. In STZ-induced diabetic mice, injection of the NPY Y2 receptor antagonist BIIE 0246 into BLA restored social novelty preference, whereas injection of BIIE 0246 into vHC was without effect. Finally, in non-diabetic mice social novelty preference was impaired by the NPY Y2 receptor agonist NPY 13-36 injected into BLA and restored by co-injection of NBQX. These results indicate that in diabetic mice glutamatergic function is enhanced in both vHC and BLA, which impairs social novelty preference through AMPA receptors. In addition, they indicate that NPYergic function in BLA, but not vHC, is enhanced in diabetic mice, which impairs social novelty preference through NPY Y2 receptors.

Increase in neuropeptide Y activity impairs social behaviour in association with glutamatergic dysregulation in diabetic mice.

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 Y2 receptor agonist NPY 13-36 into naïve mice impaired social novelty preference, but not sociability, and this effect was inhibited by the Y2 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 Y2 receptors.

Heat capacity of simple liquids in light of hydrodynamics as U(1) gauge theory.

We investigate the heat capacity of simple liquids through a theoretical approach based on a quasiparticle description. By interpreting the microscopic dynamics of particles in liquids in terms of quasiparticles, we suggest a simplified understanding of the number of degrees of freedom in liquids. A equivalence between hydrodynamics and U(1) gauge theory, which is proposed in the present paper, develops the quasiparticle description to construct a new Lagrangian which correctly reproduces the number of modes at the melting points and at the critical points. The heat capacity evaluated from this Lagrangian naturally interpolates between these two points, and agrees with the phonon theory of liquids [Sci. Rep. 2, 421 (2012)2045-232210.1038/srep00421].

GABAergic function in the lateral hypothalamus regulates feeding behavior: Possible mediation via orexin.

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 GABAA receptor agonist muscimol into the LH significantly inhibited food intake, whereas injection of the GABAA 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 GABAA receptors in the LH inhibits food intake. We next examined whether the stimulation of GABAA receptors affects hypothalamic neuropeptides that are known to regulate feeding behavior. The injection of muscimol significantly decreased preproorexin mRNA in the hypothalamus. CONCLUSION: These results indicate that food intake activates GABAergic function in the LH, which terminates feeding behavior by stimulating GABAA receptors. Moreover, it is suggested that the stimulation of GABAA receptors in the LH reduces food intake through inhibition of orexin neurons.