Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine
Fig 6
Effect of CP-601932 on the rat CT response to nicotine and ethanol.
The mean normalized CT responses at 40 mM nicotine (A) or 40% ethanol (B) in the presence and absence of varying concentrations of CP-601932 (0–0.1 mM). CP-601932 decreased the normalized tonic component of the nicotine and ethanol CT response in a dose-dependent manner. Responses at each CP-601932 concentration were fitted to response inhibition curves (see text for details). For 40 mM nicotine the fit (R2 = 0.99) yielded an inhibitor-nAChR dissociation constant (Ki) value of 34.8 nM and for 40% ethanol the fit (R2 = 0.88) gave a Ki value of 42.9 nM. These Ki values are within the range of values reported for α4β2 nAChRs [Chatterjee et al. 2011]. All mean normalized CT responses to 20 mM nicotine in the presence of CP-601932 at concentrations greater than 10−8 M were significantly smaller than the control values at p values <0.023. The p values for CP-601932 concentrations between 10−6.3 M and 10−5 M were 0.0001. The p values for CP-601932 concentrations at 10−4 M and 10−3 M were 0.0012 and 0.0055, respectively. For 40% ethanol, the p value for CP-601932 concentrations greater than 10−8 M was 0.0001 (unpaired). (C) Shows the mean normalized CT responses to 40% ethanol (ETOH) and 40 mM nicotine before and after 2h subcutaneous injection of saline (Control) or CP-601932 (10 mg/Kg body weight; Post-CP-601932). Relative to control the *p values for 40% ethanol and 40 mM nicotine were 0.0008 and 0.0005, respectively (unpaired; N = 4).