title: Distinct contributions of dopamine in the dorsolateral striatum and nucleus accumbens shell to the reinforcing properties of cocaine.
abstract: Dopaminergic neurotransmission in the dorsal and ventral striatum is thought to be involved in distinct aspects of cocaine addiction. Ventral striatal dopamine mediates the acute reinforcing properties of cocaine, whereas dopamine in the dorsolateral striatum (DLS) is thought to become involved in later stages of the addiction process to mediate well-established cue-controlled drug seeking. However, it is unclear whether the DLS also has a role in the reinforcing properties of cocaine itself. Therefore, we systematically investigated the involvement of dopamine in dorsal and ventral striatal regions in cocaine self-administration, using various schedules of reinforcement in animals with limited drug taking experience. Intra-DLS infusion of the dopamine receptor antagonist α-flupenthixol did not affect the acquisition of cocaine self-administration, increased cocaine self-administration under a fixed ratio-1 (FR-1) schedule of reinforcement, caused a rightward and downward shift of the dose-response curve of cocaine under an FR-1 schedule of reinforcement and decreased responding for cocaine under a progressive ratio (PR) schedule of reinforcement. Infusion of α-flupenthixol into the ventral nucleus accumbens (NAcc) shell inhibited the acquisition of cocaine self-administration, reduced responding for the drug under FR-1 and PR schedules of reinforcement, and caused a downward shift of the dose-response curve of cocaine self-administration under an FR-1 schedule of reinforcement. These data show that dopamine in both the DLS and NAcc shell is involved in cocaine reinforcement. We suggest that the DLS and the NAcc shell mediate somewhat distinct facets of the reinforcing properties of cocaine, related to its rewarding and motivational aspects, respectively.
authors.affiliation: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maartje M J
authors.initials: MM
authors.lastname: Veeneman
authors.forename: Mark H
authors.initials: MH
authors.lastname: Broekhoven
authors.forename: Ruth
authors.initials: R
authors.lastname: Damsteegt
authors.forename: Louk J M J
authors.initials: LJ
authors.lastname: Vanderschuren
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005475:Flupenthixol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000523:psychology
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005475:Flupenthixol; D003042:Cocaine; D004298:Dopamine