Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences

Abstract

Two of the biggest health problems facing us today are addiction to nicotine and the increased prevalence of obesity. Interestingly, nicotine attenuates obesity, but the underlying mechanism is not clear. Here we address the hypothesis that if weight-reducing actions of nicotine are mediated by anorexigenic proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus, nicotine should excite these cells. Nicotine at concentrations similar to those found in smokers, 100-1,000 nM, excited POMC cells by mechanisms based on increased spike frequency, depolarization of membrane potential, and opening of ion channels. This was mediated by activation of both α7 and α4β2 nicotinic receptors; by itself, this nicotine-mediated excitation could explain weight loss caused by nicotine. However, in control experiments nicotine also excited the orexigenic arcuate nucleus neuropeptide Y (NPY) cells. Nicotine exerted similar actions on POMC and NPY cells, with a slightly greater depolarizing action on POMC cells. Immunocytochemistry revealed cholinergic axons terminating on both cell types. Nicotine actions were direct in both cell types, with nicotine depolarizing the membrane potentials and reducing input resistance. We found no differences in the relative desensitization to nicotine between POMC and NPY neurons. Nicotine inhibited excitatory synaptic activity recorded in NPY, but not POMC, cells. Nicotine also excited hypocretin/orexin neurons that enhance cognitive arousal, but the responses were smaller than in NPY or POMC cells. Together, these results indicate that nicotine has a number of similar actions, but also a few different actions, on POMC and NPY neurons that could contribute to the weight loss associated with smoking.

Nicotinic Regulation of Energy Homeostasis

“…These results are difficult to reconcile and recall the limits of expression studies (see above). A recent paper on ex vivo preparations of ARC directly tested the electrophysiological effects of nicotine exposure on NPY neurons (Huang, Xu, & van den Pol, 2011). Nicotine at low doses directly causes NPY neuron depolarization, although it also reduced glutamatergic input to these neurons.…”

Magnesium and Zinc Involvement in Tobacco Addiction

“…The NPY is synthetised in nucleus accumbens and has receptors in this brain area. The NPY administration increased the extacellular level of nucleus accumbens dopamine [42] Nicotine at concentrations similar to those determined in heavy smokers blood plasma stimulates some NPY neurons [43]. Substances which reduced the NPY brain action diminished the dependence to other addictive compounds.…”

EKSTRAK DAUN Nicotiana tabacum MENURUNKAN BERAT LEMAK VISCERAL PADA TIKUS DIABETES MELLITUS TIPE DUA

“…28 Selain itu, berhenti merokok menormalkan nafsu makan, thermogenesis, dan mobilisasi lipid melalui aktivitas AMPK. 22 Pada penelitian yang dilakukan oleh Hosseini et al (2011) bahwa pemberian nikotin secara intraperiotenial dengan dosis kecil (0,5; 1; 1,5 mg/kgBB) menunjukkan efek peningkatan sekresi insulin.…”