Biochemical pharmacology
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Biochemical pharmacology · Oct 2013
Functional role of alpha7 nicotinic receptor in chronic neuropathic and inflammatory pain: studies in transgenic mice.
A growing body of evidence indicates that α7 nicotinic receptor subtypes play an important role in chronic inflammatory and neuropathic pain signaling. In the present study, we investigated the role of the endogenous α7 nicotinic receptors (nAChRs) signaling in pain and inflammation using transgenic mice. For that we evaluated pain-related behaviors in the α7 mutant mice (KO) and its complementary α7 hypersensitive mice (KI) expressing the L250T α7 nAChRs and their respective WT mice in acute, chronic inflammatory and neuropathic mouse models. α7 KO and KI mice showed no significant changes in pain responses evoked by acute noxious thermal and mechanical stimuli as compared with WT littermates. ⋯ Finally, the ability of systemic nicotine to reverse already-developed mechanical allodynia produced by intraplantar CFA seen in WT mice was lost in the α7 KO animals. Overall, our results demonstrate that endogenous α7 nAChRs mechanisms play an important role in chronic inflammatory and neuropathic pain models. This provides an additional rationale for the utility of α7 nAChR agonists in the treatment of inflammatory and chronic pain.
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Biochemical pharmacology · Oct 2013
Nicotinic acetylcholine receptors containing the α6 subunit contribute to ethanol activation of ventral tegmental area dopaminergic neurons.
Nicotine and alcohol are often co-abused suggesting a common mechanism of action may underlie their reinforcing properties. Both drugs acutely increase activity of ventral tegmental area (VTA) dopaminergic (DAergic) neurons, a phenomenon associated with reward behavior. Recent evidence indicates that nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels activated by ACh and nicotine, may contribute to ethanol-mediated activation of VTA DAergic neurons although the nAChR subtype(s) involved has not been fully elucidated. ⋯ Finally, pre-application of α-conotoxin MII[E11A] in WT slices reduced ethanol potentiation of ACh responses. Together our data indicate that α6-subunit containing nAChRs may contribute to ethanol activation of VTA DAergic neurons. These receptors are predominantly expressed in DAergic neurons and known to be critical for nicotine reinforcement, providing a potential common therapeutic molecular target to reduce nicotine and alcohol co-abuse.