Sensitization of rapid dopamine signaling in the nucleus accumbens core and shell after repeated cocaine in rats.
Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent K(m) of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects.
Addy
Nii A
NA
Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, USA.
Daberkow
David P
DP
Ford
Jeremy N
JN
Garris
Paul A
PA
Wightman
R Mark
RM
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D008297:Male; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine