Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals.
Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [(3)H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries.
Department of Anatomy and Neurosciences, Amsterdam Neuroscience Institute, VU university medical center, Amsterdam, The Netherlands.
Joost
J
Wiskerke
Department of Anatomy and Neurosciences, Amsterdam Neuroscience Institute, VU university medical center, Amsterdam, The Netherlands.
Anton N M
AN
Schoffelmeer
Department of Anatomy and Neurosciences, Amsterdam Neuroscience Institute, VU university medical center, Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience Institute, Faculty of Earth and Life Sciences, VU University Amsterdam,The Netherlands. Electronic address: tj.devries@vumc.nl.
Taco J
TJ
De Vries
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects*; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D003042:Cocaine; D004298:Dopamine
Dopamine; Drug addiction; Drug-induced plasticity; Natural reward; Psychostimulant; Response contingency