Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Alterations in AMPA receptor subunits and TARPs in the rat nucleus accumbens related to the formation of Ca²⁺-permeable AMPA receptors during the incubation of cocaine craving.

Neuropharmacology | Dec 19, 2011

Cue-induced cocaine seeking intensifies or incubates after withdrawal from extended access cocaine self-administration, a phenomenon termed incubation of cocaine craving. The expression of incubated craving is mediated by Ca²⁺-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). Thus, CP-AMPARs are a potential target for therapeutic intervention, making it important to understand mechanisms that govern their accumulation. Here we used subcellular fractionation and biotinylation of NAc tissue to examine the abundance and distribution of AMPAR subunits, and GluA1 phosphorylation, in the incubation model. We also studied two transmembrane AMPA receptor regulatory proteins (TARPs), γ-2 and γ-4. Our results, together with earlier findings, suggest that some of the new CP-AMPARs are synaptic. These are probably associated with γ-2, but they are loosely tethered to the PSD. Levels of GluA1 phosphorylated at serine 845 (pS845 GluA1) were significantly increased in biotinylated tissue and in an extrasynaptic membrane-enriched fraction. These results suggest that increased synaptic levels of CP-AMPARs may result in part from an increase in pS845 GluA1 in extrasynaptic membranes, given that S845 phosphorylation primes GluA1-containing AMPARs for synaptic insertion and extrasynaptic AMPARs supply the synapse. Some of the new extrasynaptic CP-AMPARs are likely associated with γ-4, rather than γ-2. The maintenance of CP-AMPARs in NAc synapses during withdrawal is accompanied by activation of CaMKII and ERK2 but not CaMKI. Overall, AMPAR plasticity in the incubation model shares some features with better described forms of synaptic plasticity, although the timing of the phenomenon and the persistence of related neuroadaptations are significantly different.

Pubmed ID: 21276808 RIS Download

Mesh terms: Animals | Behavior, Animal | Calcium Channels | Calcium Signaling | Cocaine | Cocaine-Related Disorders | Dopamine Uptake Inhibitors | Drug-Seeking Behavior | Male | Nerve Tissue Proteins | Neurons | Nucleus Accumbens | Phosphorylation | Protein Processing, Post-Translational | Protein Subunits | Protein Transport | Rats | Rats, Sprague-Dawley | Receptors, AMPA | Substance Withdrawal Syndrome

Research resources used in this publication

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDA NIH HHS, Id: R01 DA009621-14
  • Agency: NIDA NIH HHS, Id: F32 DA024502
  • Agency: NIDA NIH HHS, Id: R01 DA009621
  • Agency: NIDA NIH HHS, Id: K05 DA029099-01
  • Agency: NIDA NIH HHS, Id: K02 DA000453-10
  • Agency: NIDA NIH HHS, Id: K05 DA029099
  • Agency: NIDA NIH HHS, Id: R01 DA015835
  • Agency: NIDA NIH HHS, Id: DA004093
  • Agency: NIDA NIH HHS, Id: DA024502
  • Agency: NIDA NIH HHS, Id: R37 DA015835-09
  • Agency: NIDA NIH HHS, Id: DA09621
  • Agency: NIDA NIH HHS, Id: DA000453
  • Agency: NIDA NIH HHS, Id: DA015835
  • Agency: NIDA NIH HHS, Id: R37 DA015835
  • Agency: NIDA NIH HHS, Id: DA029099
  • Agency: NIDA NIH HHS, Id: R01 DA004093
  • Agency: NIDA NIH HHS, Id: R37 DA004093
  • Agency: NIDA NIH HHS, Id: F32 DA024502-02
  • Agency: NIDA NIH HHS, Id: K02 DA000453

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.