Novel reinforcement learning paradigm based on response patterning under interval schedules of reinforcement

There is a need to develop cognitive tasks that address valid neuropsychological constructs implicated in disease mechanisms and can be used in animals and humans to guide novel drug discovery. Present experiments aimed to characterize a novel reinforcement learning task based on a classical operant behavioral phenomenon observed in multiple species - differences in response patterning under variable (VI) vs fixed interval (FI) schedules of reinforcement. Wistar rats were trained to press a lever for food under VI30 s and later weekly test sessions were introduced with reinforcement schedule switched to FI30 s. During the FI30 s test session, post-reinforcement pauses (PRPs) gradually grew towards the end of the session reaching 22-43% of the initial values. Animals could be retrained under VI30 s conditions, and FI30 s test sessions were repeated over a period of several months without appreciable signs of a practice effect. Administration of the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 ((5S,10R)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) prior to FI30 s sessions prevented adjustment of PRPs associated with the change from VI to FI schedule. This effect was most pronounced at the highest tested dose of MK-801 and appeared to be independent of the effects of this dose on response rates. These results provide initial evidence for the possibility to use different response patterning under VI and FI schedules with equivalent reinforcement density for studying effects of drug treatment on reinforcement learning.