title: Nucleus accumbens dopamine depletion impairs both acquisition and performance of appetitive Pavlovian approach behaviour: implications for mesoaccumbens dopamine function.
abstract: The involvement of mesoaccumbens dopamine in adaptive learning and behaviour is unclear. For example, dopamine may act as a teaching signal to enable learning, or more generally modulate the behavioural expression, or selection, of an already-learned response. The present study investigated the involvement of the mesoaccumbens dopamine system in a fundamental form of learning: Pavlovian conditioning. In this case, the temporal association of a previously neutral visual stimulus and a biologically significant unconditioned stimulus (US), subsequently led to the production of the conditioned response (CR) of discriminated approach behaviour directed toward the conditioned stimulus (CS+), relative to a control (CS-) stimulus. 6-hydroxydopamine lesions of the nucleus accumbens (NAcc), leading to approximately 80% reductions in tissue dopamine, were made at varying time points in four experimental groups of rats, either before or subsequent to the acquisition of the CR. NAcc dopamine depletion produced long-term neuroadaptations in dopamine function 2 months after surgery, and profoundly impaired discriminated Pavlovian approach regardless of when the lesion was made. Thus, NAcc dopamine not only plays a role in conditioned behavioural activation, but also in making the appropriate discriminated response i.e. the direction of response. Further, acquisition lesions produced a far greater impact on discriminated approach than performance lesions. This difference in lesion-induced impairment implies that mesoaccumbens dopamine may play differential roles in the learning and performance of preparatory Pavlovian conditioning.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, Downing Street, CB2 3EB, Cambridge, UK. jap22@cam.ac.uk
authors.forename: J A
authors.initials: JA
authors.lastname: Parkinson
authors.forename: J W
authors.initials: JW
authors.lastname: Dalley
authors.forename: R N
authors.initials: RN
authors.lastname: Cardinal
authors.forename: A
authors.initials: A
authors.lastname: Bamford
authors.forename: B
authors.initials: B
authors.lastname: Fehnert
authors.forename: G
authors.initials: G
authors.lastname: Lachenal
authors.forename: N
authors.initials: N
authors.lastname: Rudarakanchana
authors.forename: K M
authors.initials: KM
authors.lastname: Halkerston
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
authors.forename: B J
authors.initials: BJ
authors.lastname: Everitt
mesh_terms: D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology*; D001245:Association Learning / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D010364:Pattern Recognition, Visual / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004298:Dopamine