Self-administration is the gold-standard for assessing reinforcement. Self-administration studies assess voluntary consumption of a compound. Safety studies examine the ability of a novel compound to maintain operant responding for drug delivery compared to vehicle and a drug of abuse from the same class or therapeutic category. Efficacy studies evaluate whether a novel compound can reduce reinforcement of a known drug of abuse. Transpharmation offers oral and intravenous self-administration using a variety of schedules of reinforcement.
Aspects of self-administration:
Acquisition
Dose-response
Drug pretreatment
Progressive ratio (motivation)
Reinstatement (model of relapse)
Acquisition of IV reinforcers
Data presented: Subjects (n=16 Male Sprague-Dawley rats) acquired appropriate discrimination between active and inactive levers for all IV reinforcers tested during daily 1 hr sessions in an operant chamber.
Acquisition of 15% Ethanol Self-administration
Data presented: Male and female Wistar rats (n=16 per sex) acquired appropriate discrimination between active and inactive levers when responding for access to 15% EtOH with and without 2% sucrose during daily 45-min sessions in an operant chamber.
Dose-response of IV reinforcers
Data presented: Male Sprague-Dawley rats (n=16 per group) modulate their behaviour and intake depending on the intravenous dose per infusion they are responding for.
Time-course data for IV reinforcer dose-response
Data presented: Male Sprague-Dawley rats (n=16 per group) modulate their behaviour and intake depending on the intravenous dose per infusion they are responding for.
IV Self-administration: Drug Pretreatment
Data presented: The smoking cessation therapy, Varenicline (α4β2 nicotinic receptor partial agonist), dose-dependently reduced responding for, and intake of, IV nicotine on a fixed ratio 2 and progressive ratio schedule of reinforcement. The 5-HT2C agonist, Lorcaserin, dose-dependently reduced responding for, and intake of, IV cocaine on a fixed ratio 2 and progressive ratio schedule of reinforcement (n=16 male Sprague-Dawley rats per reinforcer).
Drug pretreatment on Oral EtOH Self-administration
Data presented: There is emerging evidence in humans that the 5-HT receptor agonist and potent psychedelic, 5-MeO-DMT, could be effective in treating alcohol use disorder (AUD). However, this therapeutic effect has not been reproduced or systematically studied in a preclinical model.
Self-administration: Reinstatement (model of relapse)
Data presented: Reinstatement is a model of relapse wherein subjects that previously self-administered IV drug (nicotine, d-amphetamine, cocaine, heroin) undergo extinction. During extinction (i.e., Ext), subjects respond for vehicle and responding diminishes over time.
Drug pretreatment on Reinstatement
Data presented: In subjects previously trained to self-administer IV nicotine, the smoking cessation therapy Varenicline dose-dependently blocked nicotine-induced reinstatement of nicotine-seeking (n=16 male Sprague-Dawley rats).
Drug pretreatment on Reinstatement
Data presented: Male and female Sprague-Dawley rats (n=16 per sex) that first self-administered IV heroin, extinguished responding during extinction, and then tested for reinstatement.
