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The Journal of Neuroscience, October 29, 2003, 23(30):9937-9946

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Behavioral/Systems/Cognitive
Psychostimulant-Induced Plasticity of Intrinsic Neuronal Excitability in Ventral Subiculum

Donald C. Cooper, Shannon J. Moore, Nathan P. Staff, and Nelson Spruston

Department of Neurobiology and Physiology, Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208

Psychostimulant drugs such as amphetamine are prescribed to increase vigilance, suppress appetite, and treat attention disorders, but they powerfully activate the dopamine system and have serious abuse potential. Repeated psychostimulant exposure induces neuronal plasticity within the mesolimbic dopamine system. Here we present evidence that repeated amphetamine exposure results in a suppression of intrinsic neuronal excitability in the ventral subiculum, a hippocampal region that activates dopamine neurotransmission. We used patch-clamp recordings from brain slices obtained at different times after withdrawal from repeated amphetamine exposure to determine the long-term effects of amphetamine on subicular excitability. Using several postsynaptic indices of sodium channel function, our results show that excitability is decreased for days, but not weeks, after repeated amphetamine exposure. The resulting increase in action potential threshold and decrease in postsynaptic amplification of excitatory synaptic input provide the first direct evidence that psychostimulants induce plasticity of hippocampal output and suggest one mechanism by which drug withdrawal may influence limbic dopamine-dependent learning and memory.

Key words: addiction; synaptic integration; hippocampus; reward system; dopamine; behavioral sensitization; bursting; learning; memory; mesolimbic; schizophrenia; spike timing-dependent plasticity

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Received July 5, 2003; revised August 8, 2003; accepted September 4, 2003.

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