TY - JOUR
T1 - Nicotine-derived compounds as therapeutic tools against post-traumatic stress disorder
AU - Barreto, George E.
AU - Yarkov, Alexander
AU - Ávila-Rodriguez, Marcos
AU - Aliev, Gjumrakch
AU - Echeverria, Valentina
N1 - Publisher Copyright:
© 2015 Bentham Science Publishers.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after experiencing trauma. Actual therapies do not help majority of patients with PTSD. Moreover, extinguished fear memories usually reappear in the individuals when exposed to trauma cues. New drugs to reduce the impact of conditioned cues in eliciting abnormal fear responses are urgently required. Cotinine, the main metabolite of nicotine, decreased anxiety and depressive-like behavior, and enhanced fear extinction in mouse models of PTSD. Cotinine, considered a positive modulator of the α7 nicotinic acetylcholine receptor (α7nAChR), enhances fear extinction in rodents in a manner dependent on the activity of the nAChRs. Cotinine stimulates signaling pathways downstream of α7nAChR including the protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) pathway and the extracellular signal-regulated kinases (ERKs). The stimulation of these factors promotes synaptic plasticity and the extinction of fear. In this review, we discuss the hypothesis that cotinine relieves PTSD symptoms and facilitates fear memory extinction by promoting brain plasticity through the positive modulation of presynaptic nAChRs and its effectors in the brain.
AB - Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after experiencing trauma. Actual therapies do not help majority of patients with PTSD. Moreover, extinguished fear memories usually reappear in the individuals when exposed to trauma cues. New drugs to reduce the impact of conditioned cues in eliciting abnormal fear responses are urgently required. Cotinine, the main metabolite of nicotine, decreased anxiety and depressive-like behavior, and enhanced fear extinction in mouse models of PTSD. Cotinine, considered a positive modulator of the α7 nicotinic acetylcholine receptor (α7nAChR), enhances fear extinction in rodents in a manner dependent on the activity of the nAChRs. Cotinine stimulates signaling pathways downstream of α7nAChR including the protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) pathway and the extracellular signal-regulated kinases (ERKs). The stimulation of these factors promotes synaptic plasticity and the extinction of fear. In this review, we discuss the hypothesis that cotinine relieves PTSD symptoms and facilitates fear memory extinction by promoting brain plasticity through the positive modulation of presynaptic nAChRs and its effectors in the brain.
KW - Anxiety
KW - Depressive-like behavior
KW - Fear extinction
KW - Tobacco
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=84940932548&partnerID=8YFLogxK
U2 - 10.2174/1381612821666150710145250
DO - 10.2174/1381612821666150710145250
M3 - Article
C2 - 26166610
AN - SCOPUS:84940932548
SN - 1381-6128
VL - 21
SP - 3589
EP - 3595
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 25
ER -