Discriminative stimulus properties of nicotine: Further evidence for mediation at a cholinergic receptor

Abstract

Rats were trained to discriminate nicotine (0.4 mg/kg SC) from saline in a standard two-bar operant conditioning procedure with food reinforcement. The response to nicotine was dose-related and at the ED50 of 0.14 mg/kg, plasma nicotine concentrations were similar to those reported previously for cigarette smokers who inhale. The nicotine analogues anabasine and cytisine increased nicotine-appropriate responding in a dose-related manner. Animals predominantly responded on the saline-associated lever when administered drugs from a range of pharmacological classes, even at doses that were sufficiently large to reduce the overall numbers of responses. The results confirm that the nicotine discriminative stimulus is highly specific. Previous work has shown anabasine and cytisine to be active at nicotinic-cholinergic binding sites in rat brain. The finding that there is some correlation between the behavioural effects of these compounds and their actions at the nicotine binding site may indicate that the nicotine cue is mediated through a cholinergic receptor.

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

“…Additionally, ongoing research in our laboratory using 36 deliveries of sucrose on nicotine sessions is replicating this effect. Further, a similar trend was also reported by Pratt et al (1983) in a 2-lever operant drug discrimination task. We believe the increased responding at the lower test dose in our study indicates that expression of conditioned responding is slightly attenuated by an early inhibitory effect of the 0.4 mg/ kg training dose.…”

“…When different nicotine training doses are used in the operant drug discrimination literature, results are mixed as to whether rats trained on low doses of nicotine are more sensitive to the cueing effects of nicotine compared with rats trained on higher doses of nicotine. In several papers, rats trained on 0.1 mg/ kg nicotine tended to have lower ED 50 s (e.g., 0.026 mg/kg for Chance et al, 1977; 0.024 mg/kg for Desai et al, 2003; 0.02 mg/kg for Stolerman et al, 1997) than rats trained on 0.4 mg/ kg nicotine (e.g., 0.087 mg/kg for Chance et al, 1977; 0.09 mg/ kg for Gasior et al, 2002;0.14 mg/kg for Pratt et al, 1983). However, this difference is not always observed.…”

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

“…The results of these tests were generally consistent with previous operant conditioning studies and suggest the potential utility of this Pavlovian appetitive conditioning preparation in assessing the behavioral and neuropharmacological processes mediating the subjective effects of drugs. For example, the ED 50 for nicotine (0.054 mg/kg) was in the lower end of the range described for operant conditioning experiments using a 0.4 mg/kg training dose (0.05 mg/kg (Gasior et al, 1999), 0.087 mg/kg (Chance et al, 1977), and 0.14 mg/kg (Pratt et al, 1983)). The ED 50 for amphetamine (0.281 mg/kg) was also within the range described in operant drug discrimination experiments employing a 1 mg/kg training dose (0.26 mg/kg and 0.40 mg/kg (Young et al, 1998)].…”

Nicotine cue in rats: effects of central administration of ganglion‐blocking drugs

“…The procedure for establishing drug discriminations has been described in detail by Pratt et al (1983) andStolerman et al (1984) and only the main features are presented here. The rats were first trained to press bars for food reinforcers without receiving any injections.…”