Alpha1-adrenergic receptor-induced heterosynaptic long-term depression in the bed nucleus of the stria terminalis is disrupted in mouse models of affective disorders.

McElligott ZA, Winder DG
Neuropsychopharmacology. 2008 33 (10): 2313-23

PMID: 18046308 · PMCID: PMC3046390 · DOI:10.1038/sj.npp.1301635

The glutamatergic synapse in specific brain regions has been shown to be a site for convergence of stress and addictive substances. The bed nucleus of the stria terminalis (BNST), a nucleus that relays between higher order processing centers and classical reward and stress pathways, receives dense noradrenergic inputs that are known to influence behavioral paradigms of both anxiety and stress-induced relapse to drug seeking. Alpha(1)-adrenergic receptors (alpha(1)-ARs) within this region have been implicated in modulation of the HPA axis and anxiety responses. We found that application of an alpha(1)-AR agonist produced a long-term depression (LTD) of excitatory transmission in an acute mouse BNST slice preparation. This effect was mimicked by a 20 min, but not a 10 min, application of 100 microM norepinephrine (NE) in a prazosin-sensitive manner. This alpha(1)-AR LTD was independent of N-methyl-D-aspartate receptor (NMDAR) function unlike previously described alpha(1)-AR LTD in the hippocampus and visual cortex; however, it was dependent on the activation of L-type voltage gated calcium channels (VGCCs). In addition, alpha(1)-AR LTD was induced independently of the activation of mGluR5 which can also induce LTD in this region. Furthermore, alpha(1)-AR LTD was intact in mice receiving an intraperitoneal injection of cocaine but was disrupted in alpha(2a)-AR and NE transporter (NET) knockout (KO) mice. Thus a loss of this plasticity at glutamatergic synapses in BNST could contribute to affective behavioral phenotypes of these mice.

MeSH Terms (24)

Adrenergic alpha-Agonists Animals Brain Chemistry Calcium Channels, L-Type Cocaine Disease Models, Animal Dopamine Uptake Inhibitors Glutamic Acid Long-Term Synaptic Depression Male Mice Mice, Inbred C57BL Mice, Knockout Mood Disorders Neural Pathways Norepinephrine Norepinephrine Plasma Membrane Transport Proteins Organ Culture Techniques Patch-Clamp Techniques Receptors, Adrenergic, alpha-1 Receptors, Adrenergic, alpha-2 Receptors, Glutamate Septal Nuclei Synaptic Transmission

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