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Alpha‐2A adrenergic receptor activation inhibits rat hippocampal CA3 network activity
Author(s) -
Davis Kylie,
Lichter Jessica,
Nelson Brian,
Goldenstein Brianna,
Boese Sarah,
Pribula Jacqueline,
O’Brien Jasmine,
Xu Ke,
Sickler Trisha,
Green Kristan,
Jurgens Chris,
Porter James,
Doze Van
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1210
Subject(s) - hippocampal formation , agonist , inhibitory postsynaptic potential , chemistry , gabaergic , pharmacology , receptor , blockade , endocrinology , neuroscience , medicine , biology , biochemistry
Norepinephrine (NE) has potent antiepileptic properties, the pharmacology of which is unclear. Under conditions of GABAergic blockade, NE inhibits hippocampal CA3 network activity through alpha‐2 adrenergic receptor (α 2 AR) activation. This study investigated which α 2 AR subtype(s) mediate this effect. Hippocampal CA3 network activity was examined using field potential recordings in rat brain slices. The selective αAR agonist 6‐fluoroNE caused a reduction of CA3 network activity. In the presence of βAR blockade, concentration‐response curves for other AR agonists suggest that α 2 ARs mediate this response. Finally, equilibrium dissociation constants (K b ) of selective αAR antagonists were functionally determined to confirm the specific α 2 AR subtype inhibiting CA3 network activity. K b values calculated for ARC‐239, atipamezole, BRL‐44408, efaroxan, MK‐912, RS‐79948, RX‐821002 and terazosin correlated best with affinities previously determined for the α 2A AR subtype ( r = 0.96). These results indicate that, under conditions of impaired GABAergic inhibition, activation of α 2A ARs is primarily responsible for the inhibitory actions of NE in the rat hippocampal CA3 region. This study was funded in part by ND EPSCoR, NSF CAREER 0347259, NSF REU Site 0639227 and the APS Explorations in Biomedicine Undergraduate Summer Research Fellowship Program for Native Americans.