Drug Abuse Liability – Locomotor Sensitization
Repeated intermittent administration of psychostimulants (cocaine, d-amphetamine, etc.) in rodents causes a progressive increase in drug-induced locomotor activity that is higher in magnitude compared to that induced by a single injection. This phenomenon is known as locomotor sensitization. This enhanced locomotor activity is long-lasting and can be seen after a drug-free ('washout') period in response to a sub-threshold dose of the compound. The emergence of locomotor sensitization in rodents treated with a novel compound indicates potential abuse liability of the compound.
A) Mice were trained with a chronic dosing regimen of cocaine (15 mg/kg). (B) Mice were then challenged with a lower dose of cocaine (10 mg/kg) after training and a washout period of one week and showed greater locomotion in the chronic cocaine-treated group compared to the chronic vehicle-treated group.
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.
