Unpredictable saccharin reinforcement enhances locomotor responding to amphetamine

Drug-naïve, non-deprived rats were trained to lever press for saccharin under fixed-ratio (FR) or variable-ratio (VR) schedules of reinforcement. Rats trained on the VR schedule in which saccharin reinforcement was not predicted by a fixed number of lever presses subsequently showed an enhanced locomotor response to a threshold amphetamine challenge injection (0.5 mg/kg IP) administered 2 weeks following the last saccharin session. This finding suggests that chronic exposure to gambling-like conditions of uncertain reinforcement can induce neuroadaptations in brain reward systems that are similar to those produced by repeated psychostimulant exposure and may lead to the development of addictive behaviors.

► Drug-naïve rats were trained to self-administer saccharin. ► Saccharin reinforcement was either predictable or unpredictable. ► Unpredictable saccharin reinforcement produced cross-sensitization to amphetamine.