Nicotine self-administration in rats on a progressive ratio schedule of reinforcement

Donny, Eric C.; Caggiula, Anthony R.; Mielke, Michelle M.; Booth, Sheri; Gharib, Maysa; Hoffman, Alycia; Maldovan, Victoria L.; Shupenko, Craig; McCallum, Sarah E.

doi:10.1007/s002130051153

Cited by 153 publications

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“…Following the nicotine dose-response curve, rats received four sessions at the 0.03 mg/kg/infusion training dose. Rats were then allowed to respond for this dose on a PR schedule that has previously been reported by others (Depoortere et al, 1993;Donny et al, 1999); the sequence was determined using the exponential formula (5 exp(0.2 Â infusion number)À5), such that the required responses per infusion are as follows: 3,6,10,15,20,25,32,40,50,62,77,95,118,145,179,219,268,328,402,492,603. PR conditions were the same as in the FR sessions, with the exception that sessions were 2 h in duration.…”

Section: Methodsmentioning

confidence: 99%

“…The PR schedule is regarded as a valid procedure for assessing the reinforcing efficacy of drugs of abuse (Richardson and Roberts, 1996;Stafford et al, 1998), and it has been used to assess nicotine's reinforcing efficacy in laboratory animals and humans (Risner and Goldberg, 1983;Donny et al, 1999;Harvey et al, 2004). Since early onset of tobacco use is associated with a higher probability of relapse during abstinence (Cui et al, 2006), a further objective was to assess the reinstatement of nicotine seeking induced by acute reexposure to the drug (nicotine priming) in nicotine-free adult rats that were trained to self-administer nicotine either during adolescence or adulthood using the reinstatement model, an animal model of relapse to drug seeking Epstein et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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Initiation of smoking behavior typically occurs during adolescence and rarely occurs during adulthood. Despite this epidemiological evidence, relatively little is known about possible neurobiological differences in the response to nicotine in adolescents that might make them more vulnerable to nicotine addiction. In the current study, we assessed nicotine self-administration under fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in adolescent (postnatal day (P) 33-35) and adult (P91-94) rats. We then assessed extinction and reinstatement of nicotine seeking in adulthood in rats that initiated nicotine self-administration during either adolescence or adulthood. Nicotine self-administration (0.03 mg/kg/infusion, i.v.) was higher in adult rats than in adolescent rats under FR5 and PR reinforcement schedules; no age differences in nicotine self-administration were observed under FR1 or FR2 reinforcement schedules. In contrast, saccharin self-administration under FR5 and PR reinforcement schedules was similar in both age groups, potentially ruling out age differences in general performance. Rats that initiated nicotine self-administration as adults demonstrated a greater resistance to extinction of nicotine taking behavior when saline was substituted for nicotine than rats that initiated self-administration as adolescents. Reinstatement of nicotine seeking following nicotine priming injections (0.075, 0.15, 0.3 mg/kg, s.c.) was independent of the age of onset of nicotine self-administration. The present data from established rat models of drug self-administration and drug relapse suggest that nicotine is less reinforcing in adolescent compared with adult rats and that processes other than the reinforcing effects of nicotine may be involved in the greater susceptibility to smoking during the adolescent developmental stage.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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“…Rats were implanted with chronic indwelling jugular catheters after lever training. Catheters were constructed and maintained as previously described (Donny et al, 1999). Catheter patency was established with mGluR5 and nicotine reinforcement200 mg/kg infusions of chloral hydrate after the last antagonist testing sessions; rats that did not display symptoms of anesthesia within 1-min were excluded from analyses.…”

Section: Methodsmentioning

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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“…For the first 2 weeks after surgery, rats were treated with both heparin and streptokinase in order to help maintain catheter patency, and the antibiotic ticarcillan plus clavulanate to reduce post-surgical infections (see Donny et al 1999 for details). Thereafter, catheters were flushed once daily with 0.1 ml sterile heparinized saline (30 U/ml) on non-testing days (weekends), and both prior to (10 U/ml) and following (30 U/ml) each session on testing days.…”

Section: Surgerymentioning

confidence: 99%

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

et al. 2005

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Although considerable progress has been made we do not yet fully understand the behavioral and neurobiological bases of nicotine reinforcement, and without this knowledge treatment strategies aimed at reducing smoking remain deficient. This dissertation provides an original perspective on nicotine reinforcement, which arises from substantial evidence of complex interactions between nicotine and nonpharmacological stimuli. The present experiments tested the hypothesis that nicotine reinforcement derives from at least two sources: 1) the primary reinforcing properties of nicotine, an action that requires response-dependent drug administration, and 2) the more prominent ability of nicotine to enhance behavior maintained by salient non-nicotine stimuli, an action that does not require a contingent relationship between drug administration and reinforced operant responding. Although novel for nicotine, this hypothesis has origins in an extensive literature on the reinforcing properties of psychostimulant drugs. Empirical support for the application of this hypothesis to nicotine reinforcement will be presented. By investigating the interaction between nicotine and nonpharmacological stimuli within the context of drug selfadministration in rats, the present research has generated new insights into the paradox of how nicotine, an apparently weak primary reinforcer, can sustain the robust behavior observed in selfadministration and in smoking. Hypotheses generated by these data provide important direction for future investigations into the neurobiology of nicotine reinforcement.iii

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Nicotine self-administration in rats on a progressive ratio schedule of reinforcement

Abstract: Nicotine supports stable SA on a PR. Since PR and FR schedules may measure different aspects of nicotine reinforcement, PR schedules may be valuable in further characterizing group and individual differences in nicotine reinforcement.

Cited by 153 publications

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Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

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

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

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