Neural and Behavioral Plasticity Associated with the Transition from Controlled to Escalated Cocaine Use
Received 3 January 2005; received in revised form 22 April 2005; accepted 27 April 2005. published online 11 August 2005.
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 reexposed 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.
aDepartment of Psychology (Biopsychology) and Neuroscience Program, University of Michigan, Ann Arbor, Michigan
bDepartment of Psychology and Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada
Address reprint requests to Terry E. Robinson, Department of Psychology (Biopsychology) University of Michigan, East Hall, 525 East University, Ann Arbor, MI 48109-1109
ABSTRACT