Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons.
Drug seeking and drug self-administration in both animals and humans can be triggered by drugs of abuse themselves or by stressful events. Here, we demonstrate that in vivo administration of drugs of abuse with different molecular mechanisms of action as well as acute stress both increase strength at excitatory synapses on midbrain dopamine neurons. Psychoactive drugs with minimal abuse potential do not cause this change. The synaptic effects of stress, but not of cocaine, are blocked by the glucocorticoid receptor antagonist RU486. These results suggest that plasticity at excitatory synapses on dopamine neurons may be a key neural adaptation contributing to addiction and its interactions with stress and thus may be an attractive therapeutic target for reducing the risk of addiction.
Saal
Daniel
D
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Dong
Yan
Y
Bonci
Antonello
A
Malenka
Robert C
RC
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D013287:Illicit Drugs / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000209:etiology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D013287:Illicit Drugs; D018091:Receptors, AMPA; D011965:Receptors, Glucocorticoid; D016194:Receptors, N-Methyl-D-Aspartate; D015735:Mifepristone; D004298:Dopamine