TY - JOUR T1 - Extracellular-Signal Regulated Kinase 1-Dependent Metabotropic Glutamate Receptor 5-Induced Long-Term Depression in the Bed Nucleus of the Stria Terminalis Is Disrupted by Cocaine Administration JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3210 LP - 3219 DO - 10.1523/JNEUROSCI.0170-06.2006 VL - 26 IS - 12 AU - Brad A. Grueter AU - Heather B. Gosnell AU - Christopher M. Olsen AU - Nicole L. Schramm-Sapyta AU - Tanya Nekrasova AU - Gary E. Landreth AU - Danny G. Winder Y1 - 2006/03/22 UR - http://www.jneurosci.org/content/26/12/3210.abstract N2 - The bed nucleus of the stria terminalis (BNST) is a key component of the CNS stress and reward circuit. Synaptic plasticity in this region could in part underlie the persistent behavioral alterations in generalized anxiety and addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated in stress, addiction, and synaptic plasticity, but their roles in the BNST are unknown. We find that activation of group I mGluRs in the dorsal BNST induces depression of excitatory synaptic transmission through two distinct mechanisms. First, a combined activation of group I mGluRs (mGluR1 and mGluR5) induces a transient depression that is cannabinoid 1 receptor dependent. Second, as with endocannabinoid-independent group I mGluR long-term depression (LTD) in the adult hippocampus, we find that activation of mGluR5 induces an extracellular signal-regulated kinase (ERK)-dependent LTD. Surprisingly, our data demonstrate that this LTD requires the ERK1 rather than ERK2 isoform, establishing a key role for this isoform in the CNS. Finally, we find that this LTD is dramatically reduced after multiple exposures but not a single exposure to cocaine, suggesting a role for this form of plasticity in the actions of psychostimulants on anxiety and reward circuitries and their emergent control of animal behavior. ER -