Stress-induced, glucocorticoid-dependent strengthening of glutamatergic synaptic transmission in midbrain dopamine neurons.
Stress facilitates development of addictive behaviors in part by stress-induced increase in the strength of glutamatergic synapses at dopamine (DA) neurons within the ventral tegmental area (VTA). Here, we further demonstrate that this stress-induced synaptic adaptation is glucocorticoid-dependent and is progressively developed. Activation of glucocorticoid receptors (GRs) either by in vivo injection of dexamethasone (Dex) or incubation of the VTA slice with Dex potentiate the synaptic strength of glutamatergic synapses at VTA DA neurons, whereas preventing the activation of GRs by Ru486 abolishes this effect. These results suggest that the VTA GRs play a critical role in stress-induced cellular adaptations.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Shabrine S
SS
Daftary
Jaak
J
Panksepp
Yan
Y
Dong
Daniel B
DB
Saal
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*; D009435:Synaptic Transmission; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000503:physiopathology*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D018698:Glutamic Acid; D003907:Dexamethasone; D004298:Dopamine