Abstract
In the basal ganglia, convergent input and dopaminergic modulation of the direct striatonigral and the indirect striatopallidal pathways are critical in rewarding and aversive learning and drug addiction. To explore how the basal ganglia information is processed and integrated through these two pathways, we developed a reversible neurotransmission blocking technique, in which transmission of each pathway was selectively blocked by specific expression of transmission-blocking tetanus toxin in a doxycycline-dependent manner. The results indicated that the coordinated modulation of these two pathways was necessary for dopamine-mediated acute psychostimulant actions. This modulation, however, shifted to the predominant roles of the direct pathway in reward learning and cocaine sensitization and the indirect pathway in aversive behavior. These two pathways thus have distinct roles: the direct pathway critical for distinguishing associative rewarding stimuli from nonassociative ones and the indirect pathway for rapid memory formation to avoid aversive stimuli.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Adaptation, Physiological / drug effects
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Adaptation, Physiological / genetics
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Analysis of Variance
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Animals
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Avoidance Learning / drug effects
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Avoidance Learning / physiology*
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Behavior, Animal
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Central Nervous System Stimulants / pharmacology
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Cholera Toxin / metabolism
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Cocaine / pharmacology
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Conditioning, Operant / drug effects
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Corpus Striatum / cytology*
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Corpus Striatum / drug effects
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Corpus Striatum / physiology*
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Dependovirus / physiology
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Dopamine Uptake Inhibitors / pharmacology
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Doxycycline / administration & dosage
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Doxycycline / pharmacology
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Enzyme-Linked Immunosorbent Assay / methods
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Gene Expression Regulation / drug effects
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Methamphetamine / pharmacology
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Mice
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Mice, Transgenic
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Neural Pathways / physiology
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Neurons / drug effects
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Neurons / physiology
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Neurotoxins
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins / genetics
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Reward*
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Substantia Nigra / cytology
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Synaptic Transmission / physiology*
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Tetanus Toxin
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Transfection / methods
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Vesicle-Associated Membrane Protein 2 / genetics
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Vesicle-Associated Membrane Protein 2 / metabolism
Substances
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Central Nervous System Stimulants
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Dopamine Uptake Inhibitors
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Neurotoxins
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Proto-Oncogene Proteins c-fos
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RNA, Messenger
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Recombinant Fusion Proteins
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TNTCFP protein
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Tetanus Toxin
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Vesicle-Associated Membrane Protein 2
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vesicle-associated membrane protein 2, mouse
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Methamphetamine
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Cholera Toxin
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Cocaine
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Doxycycline