Age differences in the spontaneous acquisition of nicotine self-administration in male Wistar and Long–Evans rats

Shram, Megan J.; Li, Zhaoxia; Lê, A. D.

doi:10.1007/s00213-007-1003-9

Cited by 40 publications

(40 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Seven days after IV surgery, animals underwent NSA without food training ( Figure 1c) at three infusion doses (3.75, 7.5, or 15 µg/kg) that were found previously to fall along the ascending limb of nicotine's dose-response curve for spontaneous acquisition (Garcia et al, 2014). Rats underwent 2 hr daily NSA sessions under a FR1 schedule for 5 days and then a FR2 schedule for another 5 days, which was used to determine acquisition (Garcia et al, 2014;Shram et al, 2008).…”

Section: Acquisition Extinction and Reinstatementmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Garcia

Coen

Miksys

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotine-mediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 μg), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 μg/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC0-45 min were both twofold higher (p<0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75-30 μg/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 μg/kg per infusion dose, p<0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 μg/kg per infusion dose, p<0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (p<0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.

show abstract

Section: Acquisition Extinction and Reinstatementmentioning

confidence: 99%

“…Seven days after ICV cannula implant, catheters were implanted into the right jugular vein as previously described (Garcia et al, 2014;Shram et al, 2008). To maintain patency, catheters were 7 flushed daily with sterile heparin in saline (0.1 ml, 50 U/ml).…”

Section: Nicotine Self-administrationmentioning

confidence: 99%

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Garcia

Coen

Miksys

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…However, relatively little attention has been given to acquisition of self-administration at low doses. Compared with rats in early adolescence (starting PND 31), adult male rats are more likely to acquire nicotine self-administration at a low dose (15 µg/kg; Shram et al, 2008). These data are limited, however, both in terms of the age of initiation and the exclusive focus on males.…”

Section: Model Considerationsmentioning

confidence: 99%

“…At lower unit doses (3.75-10 µg/kg) on the ascending limb of the dose-response curve, mean response rates increase with dose. In this range, there is considerable individual variability in response rates and a lower proportion of rats acquire nicotine self-administration (i.e., responding greater than saline control and/or inactive operandum; Cox, Goldstein, & Nelson, 1984;Shram, Li, & Le, 2008). As such, the ascending limb of the group curve may be an averaging artifact, resulting from increasing proportions of animals acquiring, and not reflect intermediate responding by the majority of individuals.…”

Section: Dose-response Curves For Acquisition and Maintenancementioning

confidence: 99%

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

Donny

Taylor

LeSage

et al. 2012

Nicotine & Tobacco Research

View full text Add to dashboard Cite

Introduction: The Family Smoking Prevention and Tobacco Control Act in the United States and the World Health Organization Framework Convention on Tobacco or Health ratified by over 170 countries render scientific investigations into the abuse liability, harm, and effects of tobacco more critical than ever. A key area to explore relates to the potential regulation of nicotine content in cigarettes. Determining the nicotine content per cigarette below which smokers reliably reduce their consumption of and dependence on cigarettes, an idea proposed almost 20 years ago (Benowitz & Henningfield, 1994), could be a powerful approach to reduce the abuse liability and consequent harm from cigarettes. However, this approach is laden with potentially complex issues. Many of these complications can be studied using animal models, but they require a particular perspective.

show abstract

“…This prior training also creates a different pattern of responding during the acquisition period, as responding changes from food reinforcement to nicotine reinforcement. More recent self-administration studies have begun to train animals to self-administer nicotine without food (spontaneous acquisition) [7]. Without prior food training, animals respond on the nicotine-associated lever reinforced by nicotine from the start, which allows the pattern of responding during the acquisition period to be a reflection purely of nicotine reinforcement.…”

Section: Introductionmentioning

confidence: 99%

Effect of food training and training dose on nicotine self-administration in rats

Garcia

Lê

Tyndale

2014

Behavioural Brain Research

View full text Add to dashboard Cite

Few studies investigate factors that influence acquisition in nicotine self-administration (NSA), such as food training and training dose. Most have utilized peak doses along nicotine’s dose-response curve (15 and 30 μg/kg) that establish NSA in the majority of animals. To investigate the specific and combined effects of training and dose on NSA acquisition, separate and head-to head experiments using food training (FT) or spontaneous acquisition (SP) at multiple doses on the ascending limb of the dose-response curve were tested. First, rats underwent FT or SP under fixed ratio (FR1 and FR2) and progressive ratio (PR) schedules using 7.5–30 μg/kg nicotine. More rats acquired NSA with FT vs. SP at 3.75 μg/kg (56% vs. 38%) and 7.5 μg/kg (88% vs. 40%, p<0.05) and FT rats responded higher under PR. Based on these findings, rats then underwent identical NSA acquisition and PR (with and without nicotine), extinction and reinstatement induced by cue exposure and nicotine in a head-to-head comparison of FT and SP using 7.5 μg/kg. Acquisition differences were replicated: 100% FT and 60% SP rats met criteria (p<0.05). Without nicotine (cue only), no FT rats and 8% SP rats met criteria. FR and PR responding, extinction, and cue and nicotine-induced reinstatement did not differ between FT and SP. FT versus SP enhances acquisition at lower nicotine doses but does not alter subsequent behaviors. Lower doses can reinforce NSA and be used, in the absence of FT, to study influences on acquisition more closely modelling the initial phases of human smoking.

show abstract

Age differences in the spontaneous acquisition of nicotine self-administration in male Wistar and Long–Evans rats

Abstract: The current findings are consistent with those obtained under a more demanding progressive ratio reinforcement schedule and suggest that adolescents, compared to adults, may not be as sensitive to the reinforcing effects of nicotine.

Cited by 40 publications

References 79 publications

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Effect of Brain CYP2B Inhibition on Brain Nicotine Levels and Nicotine Self-Administration

Impact of Tobacco Regulation on Animal Research: New Perspectives and Opportunities

Effect of food training and training dose on nicotine self-administration in rats

Contact Info

Product

Resources

About