Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Ca²⁺-permeable AMPA receptors (CP-AMPARs) accumulate in the nucleusaccumbens (NAc) after ∼1 month of withdrawal from a long-access cocaineself-administration regimen (6 h/d, 10d). This is functionally significantbecause CP-AMPARs mediate the ‘incubated'' cue-induced cocaine craving producedby this regimen. Our present goal was to determine if other commonly employed cocaineself-administration regimens also elicit CP-AMPAR accumulation. We compared four regimens,named according to whether sessions were short-access (ShA, 2 h) or long-access(LgA, 6 h) and the total number of sessions: LgA/10d (already shown to elicitCP-AMPAR accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latterregimens, rats began with 10 days of ShA and then entered a differential phase(10–14 days) in which ShA sessions either continued or switched to LgA. Controlsself-administered saline. After >40 days of withdrawal, whole-cell patch-clamprecordings were performed in NAc core medium spiny neurons to assess the contribution ofCP-AMPAR transmission, based on the magnitude of synaptic suppression elicited by bathapplication of the selective CP-AMPAR antagonist naspm (100 μM). Naspm produceda non-significant (∼10%) attenuation of electrically evoked local excitatorypostsynaptic current in the saline and ShA groups. By contrast, a significantnaspm-induced synaptic attenuation (25–30%) was observed in both the LgAgroups. Further analyses indicate that this emergence of CP-AMPAR transmission in the LgAgroups is associated with increased baseline responsiveness of MSN to excitatory drive.Together with data on cocaine infusions in each group, our results show that CP-AMPARaccumulation and enhanced glutamate transmission is associated with longer sessions(6 h), rather than the number of sessions or cocaine infusions.