Discriminative-stimulus effects of cannabidiol oil in Sprague-Dawley rats.

Cannabidiol (CBD) is one of the major centrally active phytocannabinoid components of cannabis, and has been approved by the FDA only for the treatment of seizures associated with three rare disorders. It has also been touted as a potential treatment for anxiety in place of more traditional treatments like benzodiazepines. Although there is some evidence of anxiolytic effects of CBD, its suitability as a substitute for benzodiazepines is unknown. This experiment was designed to assess the extent to which CBD shares interoceptive discriminative-stimulus properties with the anxiolytic drug chlordiazepoxide (CDP), a benzodiazepine. In the present experiment, a range of doses (0-1569 mg/kg) of over-the-counter CBD oil was administered (i.g.) in male Sprague-Dawley rats trained to discriminate 5.6 mg/kg CDP from saline. Due to the long time-course effects of CBD, generalization tests were conducted at 90 and 120 min post-CBD administration. The two highest doses of CBD tested (1064 and 1569 mg/kg) were found to partially substitute for 5.6 mg/kg CDP, with mean percent responding on the CDP-associated lever reaching above 20% at time 2 (120 min post-CBD administration), suggesting that high doses of the over-the-counter CBD oils used in this experiment share interoceptive discriminative-stimulus properties to some degree with CDP. These results are novel in comparison to existing research into stimulus effects of CBD, in which substitution for benzodiazepines has not previously been observed.

Effects of acute and chronic nicotine administration on probability discounting.

Nicotine use is a continuing public health concern. Smokers are more likely to make risky or maladaptive decisions compared to nonsmokers, so the relation between nicotine and risky choice warrants further investigation. Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer and can be assessed through a probability-discounting procedure. Acute nicotine administration has been shown to alter risky choice, but because the everyday smoker uses nicotine repeatedly, more research on chronic administration is needed and would allow for assessment of tolerance or sensitization of any effects. The present study examined effects of acute and repeated nicotine administration on probability discounting. Sprague-Dawley rats were used as subjects and the probability-discounting task involved discrete-trial choices between a small, certain reinforcer and a larger, uncertain reinforcer. The probability of larger-reinforcer delivery decreased across blocks within each session. Acute nicotine (0.1-1.0 mg/kg) administration dose-dependently increased risky choice, increased lose-stay ratios (a measure of response perseveration), and decreased reinforcement frequency. Tolerance to nicotine's effects on larger-reinforcer choice was observed after repeated 1.0 mg/kg nicotine administration. The results of the present study add to the existing literature that acute nicotine administration increases risky choice and demonstrates that tolerance to this effect develops after chronic exposure to the drug. Possible behavioral mechanisms behind this effect are discussed, as are suggestions for future research on nicotine and risky choice.

Reduction in delay discounting due to nicotine and its attenuation by cholinergic antagonists in Lewis and Fischer 344 rats.

RATIONALE: Nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs), and mecamylamine, a nonselective nAChR antagonist, attenuates effects of nicotine on delay discounting in some rat strains; whether nicotine's attenuation is specific to nAChR antagonism is unknown. OBJECTIVE: During experiment 1, we evaluated dose-dependent effects of nicotine on delay discounting of pair-housed Lewis (LEW) and Fischer 344 (F344) rats. During experiment 2, we examined the sensitivity of nicotine's effects on delay discounting to pharmacological antagonism of nAChRs or muscarinic AChRs (mAChRs). MATERIALS AND METHODS: Male LEW and F344 were trained to choose between one food pellet delivered immediately and three food pellets delivered after an increasing delay. During experiment 1, saline and nicotine (0.1-1.0 mg/kg) were tested acutely. During experiment 2, mecamylamine (0.25-1.0 mg/kg) or a nonselective mAChR antagonist, scopolamine (0.01-0.056 mg/kg), was administered prior to nicotine administration. RESULTS: Nicotine dose dependently reduced delay discounting for both rat strains, and no strain differences were observed (ΔAUC = + 107% for 1.0 mg/kg and + 69.6% for 0.3 mg/kg relative to saline). At some doses, pretreatment with mecamylamine (range ΔAUC = - 27.6 to - 7.3%) or scopolamine (range ΔAUC = - 0.74 to - 51.6%) significantly attenuated the nicotine-induced reduction in some measures of delay discounting for both strains. CONCLUSIONS: Results from experiment 1 suggest that when LEW and F344 are pair housed, there are no strain differences in delay discounting in response to nicotine. Results from experiment 2 suggest that attenuation of nicotine's effects on delay discounting may not be specific to nAChR antagonism.

Effects of acute and repeated nicotine administration on delay discounting in Lewis and Fischer 344 rats.

Biological differences may underlie individual differences in impulsive behavior, such as choice for a smaller, more immediate reinforcer over a larger, more delayed reinforcer. Repeated exposure to drugs of abuse may have different effects on such behavior. To evaluate the acute and repeated effects of nicotine on impulsive choice, two strains of rats that have been shown to differ in impulsive choice were tested in a delay-discounting paradigm. Eight Lewis and eight Fischer 344 rats were allowed to choose between one food pellet delivered immediately and three food pellets delivered after a delay. The delay systematically increased in blocks of trials within each session, and the delay value at which the choice for the two alternatives was equal (i.e. the indifference point) was interpolated. Effects of nicotine (0.1-1.0 mg/kg, subcutaneous) on percent choice and indifference points were determined during the acute-testing phase and during the redetermination of effects of each dose after at least 30 sessions of repeated 1.0 mg/kg nicotine exposure. The Lewis rats had shorter indifference points (i.e. made fewer larger-reinforcer choices) compared with the Fischer 344 rats. Acute nicotine administration increased the mean larger-reinforcer choices at the 0.3 mg/kg dose in the Lewis rats and at the 1.0 mg/kg dose in the Fischer 344 rats. After repeated exposure to nicotine, indifference points returned to near-baseline (predrug) levels for both the strains. Strain differences were observed in the rates of delay discounting, and nicotine may decrease the impulsive choice acutely, but this effect does not seem to be long lasting.