DARPP-32 knockout mice exhibit impaired reversal learning in a discriminated operant task

The current study was conducted to examine the performance of mice with a t argeted deletion of the gene for DARPP-32 in a discriminated operant task u sing food reinforcement. DARPP-32 plays a central role in regulating the ef ficacy of dopaminergic neurotransmission. initially, wild-type and DARPP-32 knockout mice were trained to nose-poke for food on a continuous reinforce ment schedule. The minimum response requirement was increased every 5 days until the animals were responding on an FR-15 schedule of reinforcement. At the completion of extensive operant training, reversal learning was assess ed. Wild-type and DARPP-32 knockout mice exhibited equivalent performance d uring acquisition of this task, with both groups increasing operant respond ing as the schedule of reinforcement was raised. However. significant diffe rences in discrimination learning were observed during the reversal phase, with DARPP-32 knockout mice requiring significantly more trials to reach cr iterion than wild-type controls. These results provide evidence for a funct ional role of DARPP-32 in the mediation of processes underlying learning an d memory. (C) 2000 Elsevier Science B.V. All rights reserved.