Alpha2-adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o-protein-mediated modulation of Ca2+-channels and inwardly rectifying K+-channels in LTD.
Activation of adrenoreceptors modulates synaptic transmission in the basolateral amygdala. Here, we investigated the effects of alpha2-adrenoreceptor activation on long-term depression and long-term potentiation in an in vitro slice preparation of the mouse basolateral amygdala. Field potentials and excitatory postsynaptic currents were evoked in the basolateral amygdala by stimulating the lateral amygdala. Norepinephrine (20 micro m) reduced synaptic transmission and completely blocked the induction of long-term potentiation and long-term depression. The alpha2-adrenoreceptor antagonist yohimbine (2 micro m) reversed this effect. The alpha2-adrenoreceptor agonist clonidine (10 micro m) mimicked the effects of norepinephrine. The Gi/o-protein inhibitor pertussis toxin (5 micro g/mL) reversed the effect of clonidine. Long-term depression was blocked in the presence of omega-conotoxin GVIA, but not omega-agatoxin IVA. Clonidine inhibited voltage-activated Ca2+ currents mediated via N- or P/Q-type Ca2+-channels. The inhibitory action of clonidine on long-term depression was reversed when inwardly rectifying K+-channels were blocked by Ba2+ (300 micro m). The present data suggest that alpha2-adrenoreceptor activation impairs the induction of long-term depression in the basolateral amygdala by a Gi/o-protein-mediated inhibition of presynaptic N-type Ca2+-channels and activation of inwardly-rectifying K+-channels.
DeBock
F
F
Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 München, Germany.
Kurz
J
J
Azad
S C
SC
Parsons
C G
CG
Hapfelmeier
G
G
Zieglgänsberger
W
W
Rammes
G
G
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D020962:Heterotrimeric GTP-Binding Proteins / Q000145:classification / Q000378:metabolism*; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D037342:Pertussis Toxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides; D015016:Yohimbine / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007097:Imines; D007546:Isoquinolines; D010879:Piperazines; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011725:Pyridines; D018341:Receptors, Adrenergic, alpha-2; D012702:Serotonin Antagonists; D013449:Sulfonamides; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D002104:Cadmium; D005576:Colforsin; D001464:Barium; D015016:Yohimbine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C014925:RMI 12330A; D037342:Pertussis Toxin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020962:Heterotrimeric GTP-Binding Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D003000:Clonidine; D009638:Norepinephrine