Detect the dose of nicotine yet this dose did not reverse conditioned suppression as low doses did in these studies, suggesting that the effects of nicotine and DHbE on suppression ratios during CER were not due to a generalized decrement caused by statedependent learning. It is also possible that the injection itself could have served as an 4-(Benzyloxy)phenol occasion-setter to indicate that no shock would occur during these test sessions. This was not the case. Rather, saline injection led to a decrease in NON-CS responding during these test sessions, suggesting that the stress of injection led to a reduction in goal-oriented behavior as measured by lever pressing for saccharin. Several doses of nicotine, including a rewarding-like dose, reversed this suppression of NON-CS responding. Whereas it is possible that this behavior was stimulated by anxiolytic-like effects of nicotine, it is equally plausible that nicotine exposure promoted stimulus enhancing effects of the saccharin reinforcer as has been shown for an unconditioned stimulus light and a conditioned stimulus associated with an appetitive stimulus. The present results also LOUREIRIN-B showed an interesting contrast to findings using Pavlovian fear conditioning without an operant component. Unlike our observations in the CER task, systemic administration of nicotine enhances freezing in a footshock-paired context with no effect on explicit cue conditioning. These dichotomies may be due in part to the use of a more mild footshock and extended explicit cue CS training used during CER compared to traditional Pavlovian fear conditioning procedures. A significant difference in CS but not NON-CS lever pressing between mice trained to a 0.1 mA and 0.3 mA footshock suggests that the contextual fear did not contribute to CER behavior in these studies. In addition, systemic administration of DHbE alone does not affect either context or explicit cue CS-freezing following fear conditioning, drawing a further contrast between these procedures. Together these findings suggest that basic Pavlovian fear conditioning and CER are modeling different behaviors. These data further suggest that CER, but not Pavlovian fear conditioning, is sensitive to inactivation of the high affinity b2*nAChRs. Whereas the CER paradigm is a complex animal model that involves fear learning and operant behavior, this procedure benefits from subjects acting as their own controls both within and between sessions. The fact that mice showed similar effects in the marble-burying task and elevated plus maze, which do not have a learning components to them, supports the hypothesis that affective behavior was modified by nicotine and DHbE during CER. Studies in human smokers reveal that multiple factors contribute to tobacco use; as well as the pleasure received 
from smoking, many report that they use tobacco to relieve anxiety or to relax. The first cigarette of the day results in an abrupt increase in nicotine plasma concentrations that smokers associate with the rewarding effects of the drug. The nicotine ingested from a single cigarette is sufficient to occupy 80% of b2*nAChRs. During subsequent smoking episodes, smokers achieve smaller increases in nicotine that ought to preferentially favor desensitization of nAChRs if slice electrophysiology, Xenopus oocyte, tissue culture and synaptosome studies are predictive of how nAChRs function in vivo. Nicotine reaches daily steady-state concentrations in the brains of human smokers between 200�C400 nM.