Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between continuously infused and self-administered nicotine doses and serum concentrations

LeSage, Mark; Keyler, Daniel E.; Collins, G.A.; Pentel, Paul R.

doi:10.1007/s00213-003-1539-2

Cited by 74 publications

(70 citation statements)

References 42 publications

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“…Our laboratory and others have shown, using this prolonged access model (Valentine et al, 1997;Fu et al, 2001Fu et al, , 2003Brower et al, 2002;LeSage et al, 2002LeSage et al, , 2003LeSage et al, , 2006Parker et al, 2004), that adult rats will acquire nicotine SA in the absence of food deprivation or prior food-reinforced conditioning. For several reasons, this prolonged access model is advantageous for studying nicotine SA in rats during midadolescence.…”

Section: Adolescent Nicotine Self-administration H Chen Et Almentioning

confidence: 82%

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Chen

Matta

Sharp

2006

Neuropsychopharmacol

105

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As most human tobacco use begins during adolescence and ongoing development of the adolescent central nervous system could affect acquisition of nicotine self-administration (SA), our established rat SA procedure was modified to study adolescent acquisition of SA with prolonged access to nicotine (23 h/day). Postnatal age 43-45 female Lewis rats, without prior shaping, conditioning, or food deprivation, were housed in operant chambers equipped with two levers; pressing the active lever triggered an i.v. injection of nicotine. By the 10th day of SA, rats receiving 7.5, 15, 30, or 60 mg/kg/injection nicotine (free base) obtained 23716, 5078, 6578, or 4875 injections (mean7SE), respectively. In the 30 mg/kg/injection group, active : inactive ratio was greater than 2 after SA day 4; 92% of injections occurred during the 12-h active (dark) phase of the light cycle. Main effects (analysis of variance) were shown for day and lever (ie active vs inactive) (po0.001). Adolescent males showed similar dose-dependent nicotine SA. With the increasing workload imposed by raising the fixed ratio (FR), less nicotine was self-administered at FR 5 and 7 compared to FR 1 and 3. In comparison to adult females selfadministering 30 mg/kg/injection of nicotine at FR 1, adolescents acquired nicotine SA at an accelerated rate (po0.05) and received a greater number of injections (po0.05) by day 10. In conclusion, when given prolonged access to the drug, both female and male adolescent Lewis rats rapidly acquire nicotine SA within the dosage range and FR constraints previously observed in adult Lewis rats. However, adolescent females acquired the behavior more rapidly and attained higher levels of stable nicotine SA than adults.

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Section: Adolescent Nicotine Self-administration H Chen Et Almentioning

confidence: 82%

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Chen

Matta

Sharp

2006

Neuropsychopharmacol

105

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“…Finally, it is worth noting that other drugs of abuse are routinely tested for self-administration in animals via routes that are not clinically significant. While humans ingest nicotine by smoking or in smokeless tobacco [119], rats self-administer nicotine iv [40] or orally in drinking water [100].…”

Section: A Few Provisos a Couple Of Quid Pro Quosmentioning

confidence: 99%

Anabolic–androgenic steroid dependence? Insights from animals and humans

Wood

2008

Frontiers in Neuroendocrinology

136

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Anabolic-androgenic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative health consequences. As a result, in 1991 testosterone and related AAS were declared controlled substances. However, the relative abuse and dependence liability of AAS have not been fully characterized. In humans, it is difficult to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. However, using conditioned place preference and self-administration, studies in animals have demonstrated that AAS are reinforcing in a context where athletic performance is irrelevant. Furthermore, AAS share brain sites of action and neurotransmitter systems in common with other drugs of abuse. In particular, recent evidence links AAS with opioids. In humans, AAS abuse is associated with prescription opioid use. In animals, AAS overdose produces symptoms resembling opioid overdose, and AAS modify the activity of the endogenous opioid system. KeywordsAnabolic agents; Testosterone; self-administration; hamsters; drug dependence • Breakfast of champions: Recent history and prevalence of AAS useAnabolic-androgenic steroids (AAS) are a hot topic. A search of the Google news archive in March 2007 reveals 47,500 news stories on "steroids" in 2006, a 400% increase since their debut in the archive in 2002. In 2006, "steroids" even surpassed trend-setters such as "Paris Hilton" (38,500 stories) or "spinach" (42,700 stories). Current media attention on AAS abuse has been driven by accusations of steroid use among professional athletes in baseball, track, and cycling. However, public recognition of AAS use in sports dates back nearly 20 years, when Ben Johnson tested positive for stanozolol at the Seoul Olympics in 1988 [77]. Eastern Block athletes had been using steroids since the 1950's, and the International Olympic Committee banned steroid use from Olympic competition in 1976. However, the ability to reliably detect androgen metabolites in urine samples was limited until the advent of gas chromatography-mass spectroscopy [89]. Johnson's drug test spurred the United States Congress to pass the Anabolic Steroid Control Act of 1991 which declared steroids as Address all reprint requests and correspondence to Ruth I. Wood, Department of Cell and Neurobiology, Keck School of Medicine at the University of Southern California, 1333 San Pablo St., BMT 401, Los Angeles, CA 90033. Telephone (323) 442-1980, Fax: (323) 442-3466, e-mail: riw@usc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain....

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“…Although bupropion and nicotine replacement therapies are currently the most successful clinical cessation aides, when they are used in preclinical models of nicotine selfadministration they have mixed effects (Bruijnzeel and Markou, 2003;Rauhut et al, 2003;Shoaib et al, 2003) or require extreme dosing (eg LeSage et al, 2002LeSage et al, , 2003 that can sometimes interfere with ongoing behavior unrelated to nicotine seeking (Mansbach et al, 2000;Rauhut et al, 2003). One reason for this may be the complex motivational effects of nicotine; smoking (Rose et al, 2003) and nicotine selfadministration (Donny et al, 2003) are behaviors that depend on more than simple primary reinforcement by nicotine.…”

Section: Introductionmentioning

confidence: 99%

Metabotropic Glutamate 5 Receptor (mGluR5) Antagonists Decrease Nicotine Seeking, But Do Not Affect the Reinforcement Enhancing Effects of Nicotine

Palmatier

Liu

Donny

et al. 2007

Neuropsychopharmacol

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Nicotine self-administration models typically evaluate the effects of smoking cessation aides on 'primary reinforcement' engendered by nicotine. However, the more recently described reinforcement enhancing effects of the drug are not always included in experimental analyses of potential therapeutics. We evaluated the effects of pretreatment with noncompetitive antagonists of the metabotropic glutamate 5 receptor (mGluR5) on each reinforcement-related effect of nicotine using a model in which a reinforcing visual stimulus (VS) and nicotine infusions were concurrently available. Five groups (2-lever, VS-only, NIC + VS, NIC-only, or SAL-only) were instrumented for self-administration. The 2-lever group could earn a nicotine infusion (0.06 mg/kg per infusion free base) for meeting the schedule on one lever (eg right), or VS for meeting the schedule on the other lever (eg left). The VS-only group could earn VS or saline under similar contingencies. Remaining rats could press one lever to earn both reinforcers (NIC + VS), nicotine infusions (NIC-only), or saline infusions (SAL-only); the other lever was 'inactive'. Responding on the VS lever in the 2-lever group was greater than that of the VS-only group, reflecting the reinforcement-enhancing effect of nicotine. Pretreatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP) or 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) decreased nicotine intake as well as the enhanced responding for the concurrently available VS. In follow-up studies, replacing nicotine via experimenter-administered infusions sustained the drugs reinforcement enhancing effect; neither MPEP nor MTEP decreased the enhancing effects of nicotine. These findings are consistent with other studies suggesting that mGlu5 receptors mediate nicotine seeking, but do not alter the reinforcement enhancing effects of nicotine.

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Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between continuously infused and self-administered nicotine doses and serum concentrations

Abstract: Continuous nicotine infusion produced an infusion rate-related suppression of NSA that was greatest when the infusion provided nicotine doses and venous serum concentrations substantially higher than those typically associated with NRT in humans.

Cited by 74 publications

References 42 publications

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Anabolic–androgenic steroid dependence? Insights from animals and humans

Metabotropic Glutamate 5 Receptor (mGluR5) Antagonists Decrease Nicotine Seeking, But Do Not Affect the Reinforcement Enhancing Effects of Nicotine

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