Effect of transdermal nicotine replacement on alcohol responses and alcohol self-administration

Psychopharmacology (Impact Factor: 3.99). 02/2008; 196(2):189-200. DOI: 10.1007/s00213-007-0952-3

ABSTRACT RationaleNicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have examined the
effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior.

ObjectiveThe primary aim of this within-subject, double-blind study was to examine whether transdermal nicotine replacement (0mg vs
21mg/day) altered response to a low-dose priming drink and subsequent ad libitum drinking behavior.

Materials and methodsSubjects (n = 19) were non-treatment-seeking, non-dependent heavy drinkers who were daily smokers. Six hours after transdermal patch
application, subjective and physiological responses to a priming drink [designed to raise blood alcohol levels (BALs) to 0.03g/dl]
were assessed. This was followed by a 2-h self-administration period where subjects could choose to consume up to eight additional
drinks (each designed to raise BALs by 0.015g/dl) or to receive monetary reinforcement for drinks not consumed.

ResultsWe found that 6h after patch application, tobacco craving associated with withdrawal relief was decreased, and systolic blood
pressure and heart rate were increased in the active patch condition compared to the placebo patch condition. Subjective intoxication
in response to the priming drink was attenuated in the active nicotine patch condition compared to 6h of nicotine deprivation
(i.e., placebo patch). During the self-administration period, subjects had longer latencies to start drinking and consequently
appeared to consume fewer drinks when administered the active patch compared to the placebo patch.

ConclusionsIn heavy drinkers, transdermal nicotine replacement compared to mild nicotine deprivation attenuated subjective and physiological
alcohol responses and delayed the initiation of drinking.

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Available from: Stephanie S. O’Malley, Jan 02, 2015
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    • "For example , 2 recent double-blind clinical studies demonstrated that transdermal nicotine or nicotine delivered by tobacco smoke can increase alcohol consumption in men (Acheson et al., 2006; Barrett et al., 2006). In contrast, transdermal nicotine has been shown to decrease alcohol intake in women (Acheson et al., 2006) and delay alcohol drinking in heavy drinkers (McKee et al., 2008). Preclinical findings have provided further evidence that nicotine can increase ethanol (EtOH) intake (Blomqvist et al., 1996; Clark et al., 2001; Ericson et al., 2000; Lallemand et al., 2007; Le et al., 2003; Olausson et al., 2001; Potthoff et al., 1983; Smith et al., 1999), as well as decrease it (Dyr et al., 1999; Nadal et al., 1998; Sharpe and Samson, 2002) in rodents. "
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    ABSTRACT: Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at 2 different time points. Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% ethanol (EtOH) (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10 weeks of daily 1-hour sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0 mg/kg) was injected subcutaneously immediately or 4 hours prior to PSR or relapse testing. Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50 to 60 responses relapse), whereas injections of nicotine 4 hours prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0 mg/kg dose) responses on the EtOH lever during PSR and relapse tests. The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH, whereas with a delay of 4 hours, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine's metabolites (i.e., cotinine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.
    Alcoholism Clinical and Experimental Research 06/2011; 36(1):43-54. DOI:10.1111/j.1530-0277.2011.01579.x · 3.31 Impact Factor
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    • "There is recent preclinical (Steensland et al., 2007) and clinical (McKee et al., 2009) evidence to support the use of varenicline, a partial ß 2 -nAChR agonist, for reducing alcohol consumption. Additionally, the nicotine patch reduced alcohol self-administration in a human laboratory paradigm in heavy drinking daily smokers (McKee et al., 2008). Although studies examining the direct effects of ethanol on ß 2 -nAChRs are mixed (Gorbounova et al., 1998; Ribeiro-Carvalho et al., 2009; Robles and Sabria, 2008), prolonged abstinence from chronic alcohol consumption was recently associated with decreased ß 2 -nAChR availability compared to baseline in nonhuman primates (Cosgrove et al., 2010). "
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    Neuropharmacology 06/2011; 60(7-8):1318-25. DOI:10.1016/j.neuropharm.2011.01.020 · 4.82 Impact Factor
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    • "Nicotine is a major bioactive constituent of tobacco. Previous studies have shown that nicotine at low doses can improve memory functions and reduce the plaque burden, and could be used as a possible anti-Alzheimer's disease agent (Lagostena et al., 2008; McKee et al., 2008; Shim et al., 2008). Nicotine protects hippocampal neurons against the Aβ-induced apoptosis in vitro (Hellstrom-Lindahl et al., 2004). "
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    ABSTRACT: Nicotine was reported to reduce the plaque burden and could be used as a possible anti-Alzheimer's disease agent. However, the effect of nicotine on memory and tau pathology in Alzheimer's disease has been less studied. The present study investigated the effect of nicotine on tau phosphorylation and cognitive impairment induced by hippocampus injections of amyloid-beta (Abeta) 25-35. Rats were treated with nicotine hydrogen tartrate salt dissolved in normal saline by subcutaneous injection twice per day for 14 days. The age and gender matched rats treated with same amount of normal saline were used as the control. Morris water maze was used to detect the cognitive impairment induced by Abeta25-35. Compared to the sham-operated rats, Abeta25-35 injection significantly prolonged the mean escape latency in vehicle-treated rats in the Morris water maze test and increased the number of tau(pS202) and tau(pT231) immunoreactive cells. The data show that nicotine (1mg/kg in base weight) treatment significantly exacerbates cognitive impairment and tau phosphorylation at Ser-202 and Thr-231 in the hippocampus compared with Abeta25-35 injection groups in the Abeta rat model of Alzheimer's disease. The use of nicotine for treatment of Alzheimer's disease should be reassessed.
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