Drug Abuse Liability – Intravenous Self Administration
Confirmation of abuse liability is derived from training rats to self-administer an experimental compound. Rats are trained to self-administer cocaine (or another drug of abuse such as nicotine) by lever-pressing in an operant box. Once rats exhibit stable drug intake, the training drug can be substituted by an experimental compound. If the experimental drug is self-administered this indicates potential drug abuse liability. In such a case, drug-naïve rats can then be tested to assess whether the compound is self-administered in subjects that have no prior drug experience, providing stronger evidence for the abuse liability of the novel compound.
Reinforcing properties of the nAChR partial agonist varenicline (Chantix ®) in rats trained to self-administer nicotine (A) and in drug-naïve rats (B). Every infusion required 3 active lever presses, and daily test sessions lasted 1 hour. In study A, each test dose was available for four consecutive days. Asterisks indicate a significant difference from saline in A, and pound signs indicate a significant difference from saline-administering rats in B.
We have also established intravenous self-administration of morphine and cocaine at PsychoGenics. Furthermore, after extinguishing cocaine-seeking, we showed that exposure to cocaine-associated stimuli reinstated vigorous cocaine-seeking that was sensitive to the GABAB receptor agonist baclofen.
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Rats were trained to self-administer morphine or cocaine, and then allowed to self-administer various doses of morphine (A) or underwent extinction (cocaine was replaced by saline, B).
Self-administration varied as a function of morphine dose (B). Asterisks indicate significantly increased infusions compared to saline. After extinction of cocaine-seeking, rats exhibited a low level of active lever pressing (‘Ext CS’). Presentation of previously cocaine-associated stimuli (CS+) resulted in reinstatement of cocaine-seeking. Pretreatment with the GABAB receptor agonist baclofen (‘CS+ Bac’) attenuated the cocaine-seeking response. Asterisks indicate a significant difference compared to extinction, and pound sign indicates a significant difference compared to cocaine-seeking.
