A-Kinase Anchoring Protein 150 (AKAP150) Promotes Cocaine Reinstatement by Increasing AMPA Receptor Transmission in the Accumbens Shell

Neuropsychopharmacology. 2018 May;43(6):1395-1404. doi: 10.1038/npp.2017.297. Epub 2017 Dec 12.


Previous work indicated that activation of D1-like dopamine receptors (D1DRs) in the nucleus accumbens shell promoted cocaine seeking through a process involving the activation of PKA and GluA1-containing AMPA receptors (AMPARs). A-kinase anchoring proteins (AKAPs) localize PKA to AMPARs leading to enhanced phosphorylation of GluA1. AKAP150, the most well-characterized isoform, plays an important role in several forms of neuronal plasticity. However, its involvement in drug addiction has been minimally explored. Here we examine the role of AKAP150 in cocaine reinstatement, an animal model of relapse. We show that blockade of PKA binding to AKAPs in the nucleus accumbens shell of Sprague-Dawley rats attenuates reinstatement induced by either cocaine or a D1DR agonist. Moreover, this effect is specific to AKAP150, as viral overexpression of a PKA-binding deficient mutant of AKAP150 also impairs cocaine reinstatement. This viral-mediated attenuation of cocaine reinstatement was accompanied by decreased phosphorylation of GluA1-containing AMPARs and attenuated AMPAR eEPSCs. Collectively, these results suggest that AKAP150 facilitates the reinstatement of cocaine-seeking behavior by amplifying D1DR/PKA-dependent AMPA transmission in the nucleus accumbens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism*
  • Animals
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / metabolism*
  • Dietary Sucrose
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / administration & dosage
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Genetic Vectors / administration & dosage
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism
  • Recurrence
  • Self Administration
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • A Kinase Anchor Proteins
  • Akap5 protein, rat
  • Dietary Sucrose
  • Dopamine Uptake Inhibitors
  • Receptors, AMPA
  • Receptors, Dopamine D1
  • Cocaine