Parameters of self-administration of cocaine in rats under a progressive-ratio schedule

Depoortère, R.; Li, D.H.; Lane, John D.; Emmett‐Oglesby, M. W.

doi:10.1016/0091-3057(93)90503-l

Cited by 201 publications

(126 citation statements)

References 37 publications

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“…The present data demonstrate the ability of noncontingent nicotine to enhance responding for the VS using two distinct reinforcement schedules (FR and PR), which have been postulated to provide unique but complementary information on the processes that govern reinforcement. While FR schedules are thought to measure the hedonic impact of a drug, PR schedules have been used to index the motivational strength of pharmacological, natural and nonpharmacological reinforcers (Markou et al 1993;Depoortere et al 1993;Donny et al 1999;Risner and Goldberg 1983;Stafford et al 1998;McGregor and Roberts 1995;Barr and Phillips 1999;Donny et al 1999;Nicola and Deadwyler 2000). The present data suggest that regardless of contingency, nicotine can increase motivation to obtain the VS, which may reflect a corresponding increase in the incentive salience of the stimulus induced by nicotine.…”

Section: Discussionmentioning

confidence: 60%

“…Following acquisition rats were put back on an FR 1 schedule for 5 additional days (days 20-24), and then tested on a progressive ratio schedule for 3 days (days 25-27). Progressive ratio sessions lasted for 180 minutes each day, and used the formula 5xEXP(0.2xinfusion number) -5 (Depoortere et al 1993;Donny et al 1999). This formula resulted in the following sequence of required responses per reinforcer earned: 3,6,10,15,20,25,32,40,50,62,77,95,118,145,179,219,268,328.…”

Section: Self-administration Sessionsmentioning

confidence: 99%

“…PR schedules, in which the response requirements for the delivery of each consecutive reinforcement is increased during the session, provide a valuable index of how hard animals will work to obtain a reinforcer (Markou et al 1993). Consequently, they have been widely used to demonstrate the motivational impact of reinforcers on behavior (Depoortere et al 1993;Donny et al 1999;Risner and Goldberg 1983;Stafford et al 1998;Barr and Phillips 1999;Nicola and Deadwyler 2000). If nicotine increases the reinforcing strength of non-nicotine stimuli then it should also enhance motivation to obtain them.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 60%

Section: Self-administration Sessionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2005

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“…Together, these results suggest that these cocaine analogs would have psychostimulant-like abuse potential. By progressively increasing response requirement, a PR schedule measures the maximum amount of behavior that a subject emits for a reinforcer, thereby allowing a quantitative estimate of the reinforcing strength or efficacy (see Depoortere et al, 1993;Stafford et al, 1998). When measured under the present PR schedule, the order of the maximum number of injections was cocaine4WIN 354284RTI 31XRTI 51.…”

Section: Discussionmentioning

confidence: 98%

A Reduced Rate of In Vivo Dopamine Transporter Binding is Associated with Lower Relative Reinforcing Efficacy of Stimulants

Wee

2005

Neuropsychopharmacol

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A slow onset of action has been hypothesized to weaken the reinforcing effects of drugs. The present study evaluated this hypothesis with slow-onset cocaine analogs, WIN 35428, RTI 31, and RTI 51. When cocaine or a cocaine analog was made available to rhesus monkeys (n ¼ 4 or 5) for self-administration under a progressive-ratio (PR) schedule with a 1-h time-out between injections, all the drugs functioned as positive reinforcers. The maximum number of injections was in the order of cocaine4WIN 354284RTI 314RTI 51. In in vivo binding in rat striatum, equipotent doses of cocaine, WIN 35428, RTI 31, and RTI 51 were estimated to displace 25% of [ 3 H]WIN 35428 binding at the dopamine transporters (DAT), respectively, 5.8, 22.4, 30.8, and 44.1 min after the intravenous injection. Further, relative reinforcing efficacy was correlated with rate of DAT binding such that slower displacement of [ 3 H]WIN 35428 was associated with a weaker reinforcing effect. In in vitro binding in monkey brain tissue, the cocaine analogs had higher affinity for monoamine transporter sites, but similar affinity ratios of 5-HTT/DAT, compared to cocaine. Lastly, RTI 31 was shown to function as a positive reinforcer in drug-naïve rhesus monkeys under a fixed-ratio 1 schedule. Collectively, the data support the hypothesis that a slow onset at the DAT is associated with reduced reinforcing efficacy of DAT ligands. The data under both the PR and FR schedules, however, suggest that a slow onset at the DAT influence reinforcing effect only to a limited extent.

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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%

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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Parameters of self-administration of cocaine in rats under a progressive-ratio schedule

Cited by 201 publications

References 37 publications

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

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

A Reduced Rate of In Vivo Dopamine Transporter Binding is Associated with Lower Relative Reinforcing Efficacy of Stimulants

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

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