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.

Grueter BA, Gosnell HB, Olsen CM, Schramm-Sapyta NL, Nekrasova T, Landreth GE, Winder DG
J Neurosci. 2006 26 (12): 3210-9

PMID: 16554472 · PMCID: PMC6674094 · DOI:10.1523/JNEUROSCI.0170-06.2006

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.

MeSH Terms (20)

Animals Anxiety 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

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