title: A mixed fixed ratio/progressive ratio procedure reveals an apathy phenotype in the BAC HD and the z_Q175 KI mouse models of Huntington's disease.
abstract: Apathy, characterized by generally reduced interest in and likelihood to perform goal-directed actions, is a recognized symptom of Huntington's disease (HD), a devastating neurological disorder caused by a CAG repeat expansion of the Htt gene located on chromosome 4. The present experiments used a modified progressive ratio task that incorporated a fixed-ratio schedule of reinforcement component to assess consummatory behavior, and a progressive-ratio schedule component that required increasing numbers of lever-presses for successive reinforcers (0.01 ml of evaporated milk). The studies revealed an apathetic phenotype in two mouse models of HD, with decreased response rates either overall or only at higher ratio requirements in the progressive-ratio component relative to wild-type controls. Based on the procedure used (within-session fixed- and progressive-ratio components), it is proposed that an observed phenotype can be ascribed either specifically to reduced motivation to work for food reinforcement or more generally to deficits in consummatory behavior. This procedure provides a simple means to assess this type of phenotype in rodents, with issues in consummatory vs. incentive motivation reflected in general alterations in fixed- versus progressive alterations on an escalating-ratio schedules respectively, providing translational measures of the amotivation/apathy construct of the human realm to the homologous construct of incentive motivation in preclinical models of human disease.
authors.affiliation: Principal Scientist at PsychoGenics, Inc.
authors.forename: Stephen
authors.initials: S
authors.lastname: Oakeshott
authors.affiliation: Research Associate at PsychoGenics, Inc.
authors.forename: Russell
authors.initials: R
authors.lastname: Port
authors.affiliation: Research Associate at PsychoGenics, Inc.
authors.forename: Jane
authors.initials: J
authors.lastname: Cummins-Sutphen
authors.affiliation: Research Associate at PsychoGenics, Inc.
authors.forename: Jason
authors.initials: J
authors.lastname: Berger
authors.affiliation: Breeding Manager at PsychoGenics, Inc.
authors.forename: Judy
authors.initials: J
authors.lastname: Watson-Johnson
authors.affiliation: Senior Director, Neurodegenerative Disorders at PsychoGenics, Inc.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ramboz
authors.affiliation: Sr. Principal Scientist, Cognition, PsychoGenics, Inc.
authors.forename: Neil
authors.initials: N
authors.lastname: Paterson
authors.affiliation: Director of Target Biology.
authors.forename: Seung
authors.initials: S
authors.lastname: Kwak
authors.affiliation: Director of In Vivo Biology, CHDI Foundation Inc, Princeton, NJ.
authors.forename: David
authors.initials: D
authors.lastname: Howland
authors.affiliation: Senior VP Behavioral R&D at PsychoGenics, Inc.
authors.forename: Dani
authors.initials: D
authors.lastname: Brunner