title: Dopamine dependency for acquisition and performance of Pavlovian conditioned response.
abstract: During Pavlovian conditioning, pairing of a neutral conditioned stimulus (CS) with a reward leads to conditioned reward-approach responses (CRs) that are elicited by presentation of the CS. CR behaviors can be sign tracking, in which animals engage the CS, or goal tracking, in which animals go to the reward location. We investigated CR behaviors in mice with only ∼5% of normal dopamine in the striatum using a Pavlovian conditioning paradigm. These mice had severely impaired acquisition of the CR, which was ameliorated by pharmacological restoration of dopamine synthesis with l-dopa. Surprisingly, after they had learned the CR, its expression decayed only gradually in following sessions that were conducted without l-dopa treatment. To assess specific contributions of dopamine signaling in the dorsal or ventral striatum, we performed virus-mediated restoration of dopamine synthesis in completely dopamine-deficient (DD) mice. Mice with dopamine signaling only in the dorsal striatum did not acquire a CR, whereas mice with dopamine signaling only in in the ventral striatum acquired a CR. The CR in mice with dopamine signaling only in the dorsal striatum was restored by subjecting the mice to instrumental training in which they had to interact with the CS to obtain rewards. We conclude that dopamine is essential for learning and performance of CR behavior that is predominantly goal tracking. Furthermore, although dopamine signaling in the ventral striatum is sufficient to support a CR, dopamine signaling only in the dorsal striatum can also support a CR under certain circumstances.
authors.affiliation: Department of Pathology, Graduate Program in Neurobiology and Behavior, Howard Hughes Medical Institute, and Department of Biochemistry, University of Washington, Seattle, WA 98195.
authors.forename: Martin
authors.initials: M
authors.lastname: Darvas
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Wunsch
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Gibbs
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D003216:Conditioning, Operant / Q000502:physiology*; D004298:Dopamine / Q000172:deficiency / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology*; D006040:Goals; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D012201:Reward
chemical_list: D004298:Dopamine