Nicotine dosing

The 3 -hydroxycotinine/cotinine ratio (3HC/cotinine) in plasma and saliva has been evaluated as a non-invasive probe for CYP2A6 activity (Dempsey et al. 2004). The ratio was highly correlated with oral clearance of nicotine and the oral clearance and half-life of cotinine. Correlation coefficients of oral nicotine and cotinine clearances with plasma 3 -hydroxycotinine/cotinine ratios were 0.78 and 0.63, respectively, at 6 h after oral nicotine dosing. 

Ding YS, Volkow ND, Logan J, Garza V, Pappas N, King P, Fowler JS (2000) Occupancy of brain nicotinic acetylcholine receptors by nicotine doses equivalent to those obtained when smoking a cigarette. Synapse 35 234-237... 

Serotonergic systems are also affected by adolescent treatment in a sexually dimorphic manner. During adolescence, at doses that produce plasma nicotine doses similar to levels found in smokers, nicotine decreases serotonin receptors specifically in the cortex, in female rats. However, in the midbrain, there was an increase in males (Xu et al. 2002). 

Chaudhri N, Caggiula AR, et al (2007) Self-administered and noncontingent nicotine enhance reinforced operant responding in rats impact of nicotine dose and reinforcement schedule. Psychopharmacology 190(3) 353-362... 

LeSage MG, Keyler DE, Collins G, Pentel PR (2003) Effects of continuous nicotine infusion on nicotine self-administration in rats relationship between continuously infused and self-administered nicotine doses and serum concentrations. Psychopharmacology 170 278-286 Lesage MG, Burroughs D, Dufek M, Keyler DE, Pentel PR (2004) Reinstatement of nicotine selfadministration in rats by presentation of nicotine-paired stimuli, but not nicotine priming, Pharmacol Biochem Behav 79 507-513... 

Abstract Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. 

Fig. 2 a Distribution of threshold doses (in Xg kg ) for nicotine nasal spray discrimination in smokers (n = 18) vs. nonsmokers (n = 17). Horizontal lines designate group median thresholds, which did not differ between groups, b Selected subjective responses to nasal spray nicotine doses at, and just below, threshold for discrimination in smokers and nonsmokers. p < 0.05 p < 0.01 for difference between doses. Reprinted from Figs. 1 and 2 in Perkins et al. (2001c) with kind permission from Springer Science and Business Media... 

Keyler DE, Hieda Y, St Peter J, Pentel PR (1999) Altered disposition of repeated nicotine doses in rats immunized against nicotine. Nicotine Tob Res 1 241-249 Konu O, Kane JK, Barrett T, Vawter MP, Chang R, Ma JZ, Donovan DM, Sharp B, Becker KG, Li MD (2001) Region-specific transcriptional response to chronic nicotine in rat brain. Brain Res 909 194-192... 

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