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. J Neurosci 2006 Mar 22;26(12):3210-9
Date
03/24/2006Pubmed ID
16554472Pubmed Central ID
PMC6674094DOI
10.1523/JNEUROSCI.0170-06.2006Scopus ID
2-s2.0-33645236206 (requires institutional sign-in at Scopus site) 99 CitationsAbstract
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.
Author List
Grueter BA, Gosnell HB, Olsen CM, Schramm-Sapyta NL, Nekrasova T, Landreth GE, Winder DGAuthor
Christopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnxiety Disorders
Cocaine
Cocaine-Related Disorders
Disease Models, Animal
Dopamine Uptake Inhibitors
Long-Term Synaptic Depression
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinase 3
Organ Culture Techniques
Receptor, Cannabinoid, CB1
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
Reward
Septal Nuclei
Stress, Psychological
Synaptic Transmission
