Does preclinical evidence that activation of mesolimbic alpha 6 subunit containing nicotinic acetylcholine receptors support nicotine addiction phenotype?
This literature review focuses on the preclinical evidence that suggests that subclasses of β2*nAChRs that assemble with the α6 subunit may provide an effective target for tobacco cessation. α6β2*nAChRs have a highly selective pattern of neuroanatomical expression in catecholaminergic nuclei including the ventral tegmental area and its projection regions. α6β2*nAChRs promote dopamine (DA) neuron activity and DA release in the mesolimbic dopamine system, a brain circuitry that is well-studied for its contributions to addiction behavior. A combination of genetic and pharmacological studies indicates that activation of α6β2*nAChRs is necessary and sufficient for nicotine psychostimulant effects and nicotine self-administration. α6β2*nAChRs support maintenance of nicotine use, support the conditioned reinforcing effects of drug-associated cues, and regulate nicotine withdrawal.
The use of a PEEP level above the inflection point in a sepsis-induced acute lung injury animal model modulates the pulmonary and systemic inflammatory responses associated with sepsis and decreases mortality during 3 h of MV.