Nicotine deprivation

Sttuctural deficits such as those described, however, may contribute to the cognitive deficits observed in nicotine-deprived smokers (for review, see Heishman et al. 1994 Parrott et al. 1996). The differences in gray matter volumes and densities in the DLPFC between smokers and nonsmokers are of particular interest. The DLPFC plays an essential role in maintenance and manipulation of information in working memory (Callicott et al. 1999 D Esposito et al. 1999), and other cognitive domains (Richeson et al. 2003). Nicotine-deprived smokers exhibit performance deficits on tests of working memory (Mendrek et al. 2006), as well as altered activation in the DLPFC associated with working memory (Xu et al. 2005). 

Animal and human studies have demonstrated that the self-administration of palatable foods, especially sweets, increases after nicotine deprivation (Hughes et al. 1991 Ogden and Fox 1994 Spring et al. 2003). In abstinent human smokers, the reward value of carbohydrate-rich snack foods were higher in females than males, suggesting that food and nicotine may be substitutable rewards, especially for females (Spring et al. 2003). 

O Dell LE, Koob GF (2007) Nicotine deprivation effect in rats with intermittent 23-hour access to intravenous nicotine self-administration. Pharmacol Biochem Behav 86 346-353 O Dell LE, Chen SA, Smith RT, Specie SE, Balster RL, Paterson NE, Markou A, Zorrilla EP, Koob GF (2007) Extended access to nicotine self-administration leads to dependence Circadian measures, withdrawal measures, and extinction behavior in rats. J Pharmacol Exp Ther 320 180-193... 

It wasn t until the 1980s that researchers systematically replicated these smdies. The 1980s studies demonstrated unequivocally that ificotine was a potent and powerful psychoactive drug and that tobacco withdrawal was pharmacologically mediated by nicotine deprivation and modulated by environmental factors (Henningfield et al. 1985 Hughes and Hatsukami 1986). 

Because the majority of studies in this area are methodologically deficient, only studies that used placebo-control conditions and single- or double-blind drug administration procedures are included in this section. Additionally, because of the problem of interpreting nicotine-induced changes in smokers performance as discussed above, a distinction will be made between studies that administered nicotine to subjects under conditions of nicotine deprivation and no deprivation. Studies involving no nicotine deprivation include nondeprived smokers and nonsmokers. 

Sherwood et al.75 administered nicotine polacrilex gum (0 and 2 mg) three times at 1-h intervals to smokers who were overnight deprived and measured CFF after each administration. CFF threshold was increased over predose baseline after the first 2-mg dose, but no further increase after the second and third doses was observed. Thus, the initial dose appeared to reverse a deprivation-induced deficit, and subsequent doses maintained normal functioning. Baseline CFF was not measured before subjects were tobacco abstinent. No effect of nicotine on CFF was reported following administration of nicotine polacrilex or subcutaneous (SC) nicotine injections to 24-h abstinent smokers, nonabstinent smokers, and nonsmokers.76-79 The lack of effect of nicotine in the absence of nicotine deprivation is consistent with the data of Sherwood et al.,75 further suggesting that nicotine reverses withdrawal-induced deficits, but does not produce true enhancement of CFF threshold. 

In contrast to these positive effects of nicotine on memory, three studies86 93 110 reported no effect of nicotine on tests of immediate and delayed recall in nicotine-deprived smokers, and Houston et al.111 reported that immediate and delayed recall was impaired after smoking a nicotine cigarette compared to a nicotine-free cigarette. In studies of nondeprived smokers or nonsmokers, two reported that nicotine improved some aspects of memory in patients with Alzheimer s disease,77 112 two found enhanced reaction time on the Sternberg memory test,78,109 four reported no effect of nicotine on tests of immediate and delayed recall,76,77 91,113 and two found that nicotine polacrilex impaired immediate and/or delayed recall accuracy.83,114 Foulds et al.79 reported that SC nicotine enhanced response time but decreased accuracy in a digit recall test in nonsmokers. 

As discussed previously, results of studies conducted with nicotine-deprived smokers are difficult to interpret. Without pre-deprivation baseline data, which few studies report, it is difficult to conclude whether nicotine reversed deprivation-induced deficits or enhanced performance beyond that observed in the nondeprived state. In general, however, nicotine and smoking at least reversed deprivation-induced deficits in certain abilities in abstinent smokers, but such beneficial effects have not been observed consistently across a range of performance measures. For example, about half of the studies that measured sustained attention and memory reported a positive effect of nicotine however, the effects were limited to some subjects or one aspect of test performance. 

Memory impairments produced by choiine deprivation in rats are improved by nicotine (Sasaki et ai. 1991). It reduces memory deficits due to septohippocampai iesions or aged animais (Levin 1992). Nicotine s effect on memory not oniy appears after acute administration, but may persist for at least 4 weeks after the end of chronic administration (Levin et ai. 1992). 

Snyder FR, Henningfield JE. (1989). Effects of nicotine administration following 12 h of tobacco deprivation assessment on computerized performance tasks. Psychopharmacology (Berlin). 97(1) 17-22. 

Newhouse PA, Potter A, Corwin J, et al Acute nicotinic blockade produces cognitive impairment in normal humans. Psychopharmacology 108 480-484, 1992a Newhouse PA, Penetar D, Fertig J Stimulant drug effects after prolonged total sleep deprivation a comparison of amphetamine, nicotine, and deprenyl. Mil Psychol 4 207-234, 1992b... 

Cholera is a condition caused by a protein exotoxin produced by the bacterium vibrio cholerae. This protein toxin consists of six subunits one A subunit and five B subunits. The B subunits are responsible for the binding of the toxin to cAMP-functioning cells in small bowel of the intestines. The A subunit penetrates the cell and has catalytic activity which attaches the ADP portion of naturally occurring NAD (nicotine-adenosine dinucleotide) to the G-protein complex thereby inhibiting its GTPase activity. This deprives the complex of its "off-switch" for cAMP formation. The effect is the uncontrolled... 

Numerous studies investigating focused attention have used reaction time tests. Nicotine polacrilex gum (2 mg) produced faster motor reaction time, but did not affect recognition reaction time in overnight deprived smokers,75 nonabstinent smokers,76 and a group of nonabstinent smokers and nonsmokers.78 Le Houezec et al.84 found that SC nicotine (0.8 mg) increased the number of fast... 

Automobile and truck simulators have also been used in randomized studies to demonstrate the impairing effects of various doses of alcohol.78-80 Similar studies have been conducted using flight simulators.81-85 In addition, both types of simulators have been used to assess the effects of marijuana, nicotine, and other sedative medications.86-88 Simulations have also been used to examine other environmental perturbations, including sleep deprivation and elevated carbon dioxide levels.89,90... 

---