| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6264749 | Brain Research | 2011 | 12 Pages |
Glutamate signaling in prefrontal cortex and ventral tegmental area plays an important role in the molecular and behavioral plasticity associated with addiction to drugs of abuse. The current study investigated the expression and postsynaptic density redistribution of glutamate receptors and synaptic scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and ventral tegmental area after cocaine self-administration. After 14 days of extended-access (6 h/day) cocaine self-administration, rats were exposed to one of three withdrawal regimen for 10 days. Animals either stayed in home cages (Home), returned to self-administration boxes with the levers withdrawn (Box), or underwent extinction training (Extinction). Extinction training was associated with significant glutamatergic plasticity. In dorsomedial prefrontal cortex of the Extinction group, there was an increase in postsynaptic density GluR1, PSD95, and actin proteins; while postsynaptic density mGluR5 protein decreased and there was no change in NMDAR1, Homer1b/c, or PICK1 proteins. These changes were not observed in ventromedial prefrontal cortex or ventral tegmental area. In ventral tegmental area, Extinction training reversed the decreased postsynaptic density NMDAR1 protein in the Home and Box withdrawal groups. These data suggest that extinction of drug seeking is associated with selective glutamatergic plasticity in prefrontal cortex and ventral tegmental area that include modulation of receptor trafficking to postsynaptic density.
► We examined the glutamate receptor plasticity in extended-access cocaine self-administration (SA) animal model of addiction. ► Following cocaine self-administration, animals either stayed in home cages (abstinence) or lever pressing was extinguished. ► The postsynaptic density (PSD) NMDAR1 protein in VTA was decreased after abstinence but not extinction. ► An increase in PSD GluR1, PSD95, Actin and a decrease in mGluR5 receptor proteins were observed in the dorsomedial prefrontal cortex following extinction of SA. ► The glutamate receptor plasticity in PFC and VTA was region- and withdrawal-dependent.
