Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum.
A neuroanatomical principle of striatal organization has been established through which ventral domains, including the nucleus accumbens, exert control over dorsal striatal processes mediated by so-called "spiraling," striato-nigro-striatal, circuitry. We have investigated the functional significance of this circuitry in the control over a cocaine-seeking habit by using an intrastriatal disconnection procedure that combined a selective, unilateral lesion of the nucleus accumbens core and infusion of a dopamine receptor antagonist into the contralateral dorsolateral striatum, thereby disrupting striato-midbrain-striatal serial connectivity bilaterally. We show that this disconnection selectively decreased drug-seeking behavior in rats extensively trained under a second-order schedule of cocaine reinforcement. These data thereby define the importance of interactions between ventral and dorsal domains of the striatum, mediated by dopaminergic transmission, in the neural mechanisms underlying the development and performance of cocaine-seeking habits that are a key characteristic of drug addiction.
Belin
David
D
Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK. bdb26@cam.ac.uk
Everitt
Barry J
BJ
D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000209:etiology / Q000473:pathology / Q000523:psychology; D001522:Behavior, Animal; D003042:Cocaine / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000150:complications* / Q000209:etiology; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005475:Flupenthixol / Q000494:pharmacology; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D012646:Self Administration / Q000379:methods
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005475:Flupenthixol; D003042:Cocaine; D004298:Dopamine