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The Journal of Neuroscience, October 25, 2006, 26(43):11041-11051; doi:10.1523/JNEUROSCI.2898-06.2006
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Behavioral/Systems/Cognitive
Amphetamine-Induced Place Preference and Conditioned Motor Sensitization Requires Activation of Tyrosine Kinase Receptors in the Hippocampus
Fei Shen,1 Gloria E. Meredith,2 andT. Celeste Napier1 1Neuroscience Program and Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Medical Center, Maywood, Illinois 60153, and 2Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064
Correspondence should be addressed to Fei Shen, Department of Pharmacology and Experimental Therapeutics, Building 102, Room 3639, Loyola University Chicago Medical Center, 2160 South 1st Avenue, Maywood, IL 60153. Email: fshen{at}lumc.edu
The environmental context in which abused drugs are taken contribute to the drug experience and is a powerful and persistent stimulus to elicit memories of that experience even in the abstinent addict. Using amphetamine (AMPH) as the unconditioned stimulus, the present study compared two popular context-dependent paradigms in rats, conditioned motor sensitization (CMS) and conditioned place preference (CPP), to ascertain whether particular brain regions were differentially involved. The neuronal substrates underlying these context-dependent behaviors are poorly understood, but regulators of the neuronal plasticity that accompany learning, such as neurotrophic factors and their cognate tyrosine kinase receptors (e.g., TrkB), are credible candidates. We found a significant elevation of TrkB-like immunoreactivity specifically in CA3/dentate gyrus (DG) subregions of the hippocampus after AMPH (0.3 mg/kg)-induced CPP, but not in the delayed-paired (control) AMPH condition. A higher AMPH dose (1.0 mg/kg) induced both CPP and CMS and elevated TrkB in the CA3/DG as well as in the nucleus accumbens shell. The development of both conditioned behaviors was blocked by intra-CA3/DG infusion of the Trk inhibitor K-252a. These findings reveal that CPP and CMS are induced by different doses of AMPH and are associated with TrkB changes in particular brain regions. Moreover, Trk receptors in the hippocampus are critical mediators of the neuronal changes necessary for inducing both forms of conditioning. Thus, although these two conditioning models are distinct, because they are commonly regulated by the hippocampal Trk system, these receptors may be a therapeutic target for attenuating the significance of contextual cues that otherwise strengthen the addictive properties of abused drugs.
Key words: rat; TrkB; BDNF; psychostimulant; associative learning; behavioral sensitization
Received Feb. 19, 2006; revised Aug. 19, 2006; accepted Aug. 20, 2006.
Correspondence should be addressed to Fei Shen, Department of Pharmacology and Experimental Therapeutics, Building 102, Room 3639, Loyola University Chicago Medical Center, 2160 South 1st Avenue, Maywood, IL 60153. Email: fshen{at}lumc.edu
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[Abstract] [Full Text] [PDF]
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