?4?6?2* nAChR Activation on VTA DA Neurons Is Sufficient to Stimulate a Depolarizing Conductance and Enhance Surface AMPA Receptor Function.

?4?6?2* nAChR Activation on VTA DA Neurons is Sufficient to Stimulate a Depolarizing Conductance and Enhance Surface AMPA Receptor Function.

Mol Pharmacol. 2013 Jun 20;
Engle SE, Shih PY, McIntosh JM, Drenan RM

Tobacco addiction is a serious threat to public health in the United States and abroad, and development of new therapeutic approaches is a major priority. Nicotine activates and/or desensitizes nicotinic acetylcholine receptors (nAChRs) throughout the brain. nAChRs in ventral tegmental area (VTA) dopamine (DA) neurons are crucial for the rewarding and reinforcing properties of nicotine in rodents, suggesting that they may be key mediators of nicotine’s action in humans. However, which nAChR subtype(s) that is/are sufficient to activate these neurons is unknown. To test the hypothesis that nAChRs containing ?6 subunits are sufficient to activate VTA DA neurons, we studied mice expressing hypersensitive, gain-of-function ?6 nAChRs (?6L9’S mice). In voltage clamp recordings in brain slices from adult mice, 100 nM nicotine was sufficient to elicit inward currents in VTA DA neurons via ?6?2* nAChRs. In addition, we found that low concentrations of nicotine could act selectively through ?6?2* nAChRs to enhance the function of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors on the surface of these cells. In contrast, ?6?2* activation did not enhance N-methyl D-aspartic acid (NMDA) receptor function. Finally, AMPAR function was not similarly enhanced in brain slices from ?6L9’S mice lacking ?4 nAChR subunits, suggesting that ?4?6?2* nAChRs are important for enhancing AMPAR function in VTA DA neurons. Together, these data suggest that activation of ?4?6?2* nAChRs in VTA DA neurons is sufficient to support the initiation of cellular changes that play a role in addiction to nicotine. ?4?6?2* nAChRs may be a promising target for future smoking cessation pharmacotherapy. HubMed – addiction



Georgian Med News. 2013 May; 82-85
Kikalishvili B, Zurabashvili D, Turabelidze D, Shanidze L, Nikolaishvili M

Using high-performance liquid chromatography methods (Cromatograph PTC-1, repractometer R-401, column Bondopa? C18) were quantitatively and qualitatively identified most biological important high fatty acids, contained in peach oil (Persica Vulgaris) from ost region of Georgia (Kacheti). Their relative concentrations are expressed as percentages of the total fatty acids components. The chromatography investigation shaved, that the oil contained 12,98±1,0mg% linoleic, 9,97±0,3 mg% palmitic, 4,82±0,2 mg% linolenic, 3,58±0,1 mg% begenic and 2,16±0,1 mg% arachinic acids. The predominant fatty acids of peach oil were linoleic, palmitic and oleinic acids. The investigation showed different sensitivity of components contained in peach oil. HubMed – addiction


The European Monitoring Centre for Drugs and Drug Addiction publishes the European Drug Report 2013: Trends and developments.

Euro Surveill. 2013; 18(22):

HubMed – addiction