The role of dorsal vs ventral striatal pathways in cocaine-seeking behavior after prolonged abstinence in rats
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Recent studies have implicated an important role for the dorsal striatum during craving for cocaine and in cocaine-seeking after abstinence in rats.
We compared the effects of pharmacological inactivation of mesencephalic dopamine (DA) cell body regions and dorsal vs ventral striatal terminal fields in an animal model of relapse after chronic cocaine self-administration.
Materials and methods
Rats self-administered cocaine for 2 h/day for ten sessions, followed by 2 weeks of abstinence (i.e., no extinction training). Immediately before being returned to the self-administration chamber, we assessed the effects of gamma-aminobutyric acid agonist inhibition of midbrain DA regions (substantia nigra [SN] and ventral tegmental area [VTA]) and striatum (dorsolateral caudate–putamen, nucleus accumbens core, and nucleus accumbens shell) on relapse to cocaine-seeking in the absence of reinforcement. Further testing examined daily extinction responding subsequent to the initial relapse test.
Inactivation of the dorsal caudate–putamen and midbrain regions attenuated cocaine seeking, while inactivation of the ventral striatum had no such effects. However, subsequent sessions under extinction conditions revealed a rebound in cocaine seeking in animals that had undergone inactivation in all regions except the dorsolateral caudate–putamen.
The dorsal but not ventral striatum plays a critical role in cocaine seeking immediately after abstinence. These data support the theory that chronic cocaine may shift activity from the ventral to dorsal striatum during drug seeking under certain conditions. While not necessary at the time of relapse, the ventral striatum appears to be involved in processing critical information of the relapse event.
KeywordsCocaine Extinction Reinstatement Relapse Self-administration Striatum
We thank Ritu Mehta and Alisha Henderson for providing excellent technical assistance. This research was supported by National Institute on Drug Abuse grants DA10462 and DA15369 and NIH grant C06 RR015455.
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