title: DARPP-32 knockout mice exhibit impaired reversal learning in a discriminated operant task.
abstract: The current study was conducted to examine the performance of mice with a targeted deletion of the gene for DARPP-32 in a discriminated operant task using food reinforcement. DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission. Initially, wild-type and DARPP-32 knockout mice were trained to nose-poke for food on a continuous reinforcement 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 assessed. Wild-type and DARPP-32 knockout mice exhibited equivalent performance during acquisition of this task, with both groups increasing operant responding as the schedule of reinforcement was raised. However, significant differences in discrimination learning were observed during the reversal phase, with DARPP-32 knockout mice requiring significantly more trials to reach criterion than wild-type controls. These results provide evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory.
authors.affiliation: Department of Psychology, Franklin and Marshall College, P.O. Box 3003, Lancaster, PA 17604, USA. c_heyser@acad.fandm.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Heyser
authors.forename: A A
authors.initials: AA
authors.lastname: Fienberg
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: L H
authors.initials: LH
authors.lastname: Gold
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology*; D004193:Discrimination Learning / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000235:genetics*; D012193:Reversal Learning / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D004298:Dopamine