We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Calcium-Permeable AMPA Receptors in the Nucleus Accumbens Regulate Depression-Like Behaviors in the Chronic Neuropathic Pain State.
- Authors
Goffer, Yossef; Duo Xu; Eberle, Sarah E.; D'amour, James; Lee, Michelle; Tukey, David; Froemke, Robert C.; Ziff, Edward B.; Jing Wang
- Abstract
Depression is a salient emotional feature of chronic pain. Depression alters the pain threshold and impairs functional recovery. To date, however, there has been limited understanding of synaptic or circuit mechanisms that regulate depression in the pain state. Here, we demonstrate that depression-like behaviors are induced in a rat model of chronic neuropathic pain. Using this model, we show that chronic pain selectively increases the level of GluA 1 subunits of AMPA-type glutamate receptors at the synapses of the nucleus accumbens (NAc), a key component of the brain reward system. We find, in addition, that this increase in GluAl levels leads to the formation of calcium-permeable AMPA receptors (CPARs). Surprisingly, pharmacologic blockade of these CPARs in the NAc increases depression-like behaviors associated with pain. Consistent with these findings, an AMPA receptor potentiator delivered into the NAc decreases pain-induced depression. These results show that transmission through CPARs in the NAc represents a novel molecular mechanism modulating the depressive symptoms of pain, and thus CPARs may be a promising therapeutic target for the treatment of pain-induced depression. More generally, these findings highlight the role of central glutamate signaling in pain states and define the brain reward system as an important region for the regulation of depressive symptoms of pain.
- Subjects
MENTAL depression risk factors; CHRONIC pain; NEUROLOGICAL disorders; NUCLEUS accumbens; AMPA receptors
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 48, p19034
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2454-13.2013