Enhanced inhibition of synaptic transmission by dopamine in the nucleus accumbens during behavioral sensitization to cocaine.
Neural adaptations in the nucleus accumbens (NAc), a key component of the mesolimbic dopamine (DA) system, are thought to mediate several of the long-term behavioral sequelas of chronic in vivo exposure to drugs of abuse. Here, we examine whether the modulation of excitatory synaptic transmission by DA in the NAc shell is modified after chronic cocaine exposure that induced behavioral sensitization. The DA-induced inhibition of AMPA receptor-mediated synaptic responses was enhanced in cocaine-treated mice, an effect that was caused by activation of D1-like receptors. DA did not enhance NMDA receptor-mediated synaptic responses in saline- and cocaine-treated mice or in the dorsal striatum of control mice. We hypothesize that the enhanced inhibitory effects of DA on synaptic transmission in the NAc are one of a number of adaptations that contribute to a decrease in excitatory drive to NAc after exposure to drugs of abuse.
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 94304, USA.
Corinne
C
Beurrier
Robert C
RC
Malenka
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013995:Time
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D003042:Cocaine; D004298:Dopamine