PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior

Autor: Hita Adwanikar, Cara Ramsey, Yu Fu, Jeong Han, Volker Neugebauer, Titilope A. Ishola, Michelle Scerbo
Rok vydání: 2008
Předmět:
MAPK/ERK pathway
Male
Indoles
Striatum
Synaptic Transmission
Maleimides
Rats
Sprague-Dawley
0302 clinical medicine
Cyclic AMP
Extracellular Signal-Regulated MAP Kinases
Protein Kinase C
Neurons
0303 health sciences
Neuronal Plasticity
Central nucleus of the amygdala
Glutamate receptor
Amygdala
Molecular Medicine
NMDA receptor
lcsh:RB1-214
medicine.medical_specialty
Neural facilitation
Carbazoles
Pain
Biology
Neurotransmission
Receptors
N-Methyl-D-Aspartate
03 medical and health sciences
Cellular and Molecular Neuroscience
Internal medicine
Nitriles
medicine
lcsh:Pathology
Butadienes
Animals
Pyrroles
Protein Kinase Inhibitors
030304 developmental biology
Behavior
Arthritis
Research
Colforsin
Thionucleotides
Cyclic AMP-Dependent Protein Kinases
Rats
Enzyme Activation
Disease Models
Animal
Anesthesiology and Pain Medicine
Endocrinology
Synaptic plasticity
030217 neurology & neurosurgery
Zdroj: Molecular Pain
Molecular Pain, Vol 4, Iss 1, p 26 (2008)
ISSN: 1744-8069
Popis: The laterocapsular division of the central nucleus of the amygdala (CeLC) has emerged as an important site of pain-related plasticity and pain modulation. Glutamate and neuropeptide receptors in the CeLC contribute to synaptic and behavioral changes in the arthritis pain model, but the intracellular signaling pathways remain to be determined. This study addressed the role of PKA, PKC, and ERK in the CeLC. Adult male Sprague-Dawley rats were used in all experiments. Whole-cell patch-clamp recordings of CeLC neurons were made in brain slices from normal rats and from rats with a kaolin/carrageenan-induced monoarthritis in the knee (6 h postinduction). Membrane-permeable inhibitors of PKA (KT5720, 1 microM; cAMPS-Rp, 10 microM) and ERK (U0126, 1 microM) activation inhibited synaptic plasticity in slices from arthritic rats but had no effect on normal transmission in control slices. A PKC inhibitor (GF109203x, 1 microM) and an inactive structural analogue of U0126 (U0124, 1 microM) had no effect. The NMDA receptor-mediated synaptic component was inhibited by KT5720 or U0126; their combined application had additive effects. U0126 did not inhibit synaptic facilitation by forskolin-induced PKA-activation. Administration of KT5720 (100 microM, concentration in microdialysis probe) or U0126 (100 microM) into the CeLC, but not striatum (placement control), inhibited audible and ultrasonic vocalizations and spinal reflexes of arthritic rats but had no effect in normal animals. GF109203x (100 microM) and U0124 (100 microM) did not affect pain behavior. The data suggest that in the amygdala PKA and ERK, but not PKC, contribute to pain-related synaptic facilitation and behavior by increasing NMDA receptor function through independent signaling pathways.
Databáze: OpenAIRE
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