Eur J Pharmacol 2005 Dec;526(1-3):65-76
Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Cocaine addiction in human addicts is characterized by a high rate of relapse following successful detoxification. Relapse to drug taking/seeking can be precipitated by several stimuli including, but not limited to, re-exposure to cocaine itself. In order to understand the mechanisms underlying cocaine craving, a substantial effort has been devoted to elucidating the anatomical and neurochemical bases underlying cocaine priming-induced reinstatement, an animal model of relapse. Here, we review evidence that changes in dopaminergic and glutamatergic transmission in limbic/basal ganglia circuits of interconnected nuclei including the medial prefrontal cortex, nucleus accumbens, ventral pallidum, amygdala, hippocampus, orbitofrontal cortex, neostriatum and thalamus underlie cocaine priming-induced reinstatement of cocaine seeking. Maladaptive changes in the processing of motivationally relevant stimuli by these circuits following cocaine self-administration result in drug craving and compulsive drug seeking upon re-exposure to cocaine.