Extinction of cocaine self-administration reveals functionally and temporally distinct dopaminergic signals in the nucleus accumbens.
While Pavlovian and operant conditioning influence drug-seeking behavior, the role of rapid dopamine signaling in modulating these processes is unknown. During self-administration of cocaine, two dopaminergic signals, measured with 100 ms resolution, occurred immediately before and after the lever press (termed pre- and post-response dopamine transients). Extinction of self-administration revealed that these two signals were functionally distinct. Pre-response transients, which could reflect the motivation to obtain the drug, did not decline during extinction. Remarkably, post-response dopamine transients attenuated as extinction progressed, suggesting that they encode the learned association between environmental cues and cocaine. A third type of dopamine transient, not time locked to overt stimuli, decreased in frequency during extinction and correlated with calculated cocaine concentrations. These results show that dopamine release transients involved in different aspects of cocaine self-administration are highly plastic--differentially governed by motivation, learned associations linked with environmental stimuli, and the pharmacological actions of cocaine.
Stuber
Garret D
GD
Curriculum in Neurobiology, The University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Wightman
R Mark
RM
Carelli
Regina M
RM
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D016014:Linear Models; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000528:radiation effects; D010082:Oxepins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D013997:Time Factors
C461941:1-phenyl-1,4-epoxy-1H,4H-naphtho(1,8-de)(1,2)dioxepin; D018765:Dopamine Uptake Inhibitors; D009281:Naphthalenes; D010082:Oxepins; D003042:Cocaine; D004298:Dopamine