TY - JOUR
T1 - Hierarchical recruitment of phasic dopamine signaling in the striatum during the progression of cocaine use
AU - Willuhn, Ingo
AU - Burgeno, Lauren M.
AU - Everitt, Barry J.
AU - Phillips, Paul E. M.
PY - 2012
Y1 - 2012
N2 - Drug addiction is a neuropsychiatric disorder that marks the end stage of a progression beginning with recreational drug taking but culminating in habitual and compulsive drug use. This progression is considered to reflect transitions among multiple neural loci. Dopamine neurotransmission in the ventromedial striatum (VMS) is pivotal in the control of initial drug use, but emerging evidence indicates that once drug use is well established, its control is dominated by the dorsolateral striatum (DLS). In the current work, we conducted longitudinal neurochemical recordings to ascertain the spatiotemporal profile of striatal dopamine release and to investigate how it changes during the period from initial to established drug use. Dopamine release was detected using fast-scan cyclic voltammetry simultaneously in the VMS and DLS of rats bearing indwelling i.v. catheters over the course of 3 wk of cocaine self-administration. We found that phasic dopamine release in DLS emerged progressively during drug taking over the course of weeks, a period during which VMS dopamine signaling declined. This emergent dopamine signaling in the DLS mediated discriminated behavior to obtain drug but did not promote escalated or compulsive drug use. We also demonstrate that this recruitment of dopamine signaling in the DLS is dependent on antecedent activity in VMS circuitry. Thus, the current findings identify a striatal hierarchy that is instantiated during the expression of established responses to obtain cocaine
AB - Drug addiction is a neuropsychiatric disorder that marks the end stage of a progression beginning with recreational drug taking but culminating in habitual and compulsive drug use. This progression is considered to reflect transitions among multiple neural loci. Dopamine neurotransmission in the ventromedial striatum (VMS) is pivotal in the control of initial drug use, but emerging evidence indicates that once drug use is well established, its control is dominated by the dorsolateral striatum (DLS). In the current work, we conducted longitudinal neurochemical recordings to ascertain the spatiotemporal profile of striatal dopamine release and to investigate how it changes during the period from initial to established drug use. Dopamine release was detected using fast-scan cyclic voltammetry simultaneously in the VMS and DLS of rats bearing indwelling i.v. catheters over the course of 3 wk of cocaine self-administration. We found that phasic dopamine release in DLS emerged progressively during drug taking over the course of weeks, a period during which VMS dopamine signaling declined. This emergent dopamine signaling in the DLS mediated discriminated behavior to obtain drug but did not promote escalated or compulsive drug use. We also demonstrate that this recruitment of dopamine signaling in the DLS is dependent on antecedent activity in VMS circuitry. Thus, the current findings identify a striatal hierarchy that is instantiated during the expression of established responses to obtain cocaine
U2 - https://doi.org/10.1073/pnas.1213460109
DO - https://doi.org/10.1073/pnas.1213460109
M3 - Article
C2 - 23184975
SN - 0027-8424
VL - 109
SP - 20703
EP - 20708
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 50
ER -