Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use.
BACKGROUND
Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction.


METHODS
Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies.


RESULTS
When re-exposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex).


CONCLUSIONS
The transition from stable to escalated cocaine use, a hallmark of addiction, is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.
Ferrario
Carrie R
CR
Department of Psychology (Biopsychology) and Neuroscience Program, University of Michigan, Ann Arbor, MIichigan 48109-1109, USA.
Gorny
Grazyna
G
Crombag
Hans S
HS
Li
Yilin
Y
Kolb
Bryan
B
Robinson
Terry E
TE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D019416:Head Movements / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D013239:Stereotyped Behavior / Q000187:drug effects
D003042:Cocaine