Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats

• Published in: Psychopharmacologia 2009-09, Vol.205 (4), p.655-665
• Main Authors: Murray, Jennifer E., Wells, Nicole R., Lyford, George D., Bevins, Rick A.
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Animals; Antagonist drugs; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Conditioning, Classical - drug effects; Conditioning, Classical - physiology; Cyclohexanols - pharmacology; Discrimination Learning - drug effects; Discrimination Learning - physiology; Drug Interactions; Male; Medical sciences; Neurosciences; Nicotine; Nicotine - pharmacology; Original Investigation; Pharmacology/Toxicology; Piperidines - pharmacology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Pyrazoles - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - physiology; Rodents; Smoking cessation; Tobacco smoking; Tobacco, tobacco smoking; Toxicology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1572-x

Rationale The cannabinoid CB 1 receptor antagonist/inverse agonist rimonabant (SR 141716) has been shown to block reinforcing and rewarding effects of nicotine. Research has not investigated whether the cannabinoid system is involved in the interoceptive stimulus effects of nicotine functioning as a conditional stimulus (CS). Objective We examined the effects of rimonabant and the CB 1/2 receptor agonist, CP 55,940, on responding evoked by a nicotine CS in rats. Additionally, we determined whether CP 55,940 functioned as a CS or a Pavlovian positive drug feature Materials and methods Pavlovian discrimination training involved intermixed nicotine (0.2 mg base/kg) and saline sessions with intermittent access to water only on nicotine. Antagonism tests with rimonabant (0.1-3 mg/kg) and substitution tests with CP 55,940 (0.003–0.1 mg/kg) followed. An effective dose of CP 55,940 was tested against the nicotine generalization curve. A separate group received CS training with CP 55,940 (0.01 mg/kg). Two other groups were trained using CP 55,940 (0.01 or 0.03 mg/kg) as a positive drug feature in which a brief light CS signaled access to water only on CP 55,940 sessions Results Rimonabant blocked nicotine-evoked responding. CP 55,940 partially substituted for nicotine and enhanced responding to lower nicotine doses. Overall, CP 55,940 did not acquire control of conditioned responding in either Pavlovian drug discrimination task Conclusions The cannabinoid system was involved in the CS effects of nicotine. This finding is counter to the operant drug discrimination research with nicotine as a discriminative stimulus, warranting further research into this possible dissociation.