Premium
The role of the serotonin transporter in prefrontal cortex glutamatergic signaling following short‐ and long‐access cocaine self‐administration
Author(s) -
Caffino Lucia,
Mottarlini Francesca,
Van Reijmersdal Boyd,
Telese Francesca,
Verheij Michel M.M.,
Fumagalli Fabio,
Homberg Judith R.
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12896
Subject(s) - infralimbic cortex , prefrontal cortex , glutamate receptor , serotonin transporter , glutamatergic , nmda receptor , neuroscience , postsynaptic potential , postsynaptic density , neurotransmission , serotonin , endocrinology , knockout mouse , medicine , biology , receptor , cognition
Vulnerability to drug addiction relies on substantial individual differences. We previously demonstrated that serotonin transporter knockout (SERT −/− ) rats show increased cocaine intake and develop signs of compulsivity. However, the underlying neural mechanisms are not fully understood. Given the pivotal role of glutamate and prefrontal cortex in cocaine‐seeking behavior, we sought to investigate the expression of proteins implicated in glutamate neurotransmission in the prefrontal cortex of naïve and cocaine‐exposed rats lacking SERT. We focused on the infralimbic (ILc) and prelimbic (PLc) cortices, which are theorized to exert opposing effects on the control over subcortical brain areas. SERT −/− rats, which compared to wild‐type (SERT +/+ ) rats show increased ShA and LgA intake short‐access (ShA) and long‐access (LgA) cocaine intake, were sacrificed 24 h into withdrawal for ex vivo molecular analyses. In the ILc homogenate of SERT −/− rats, we observed a sharp increase in glial glutamate transporter 1 (GLT‐1) after ShA, but not LgA, cocaine intake. This was paralleled by ShA‐induced increases in GluN1, GluN2A, and GluN2B NMDA receptor subunits and their scaffolding protein SAP102 in the ILc homogenate, but not postsynaptic density, of these knockout animals. In the PLc, we found no major changes in the homogenate; conversely, the expression of GluN1 and GluN2A NMDA receptor subunits was increased in the postsynaptic density under ShA conditions and reduced under LgA conditions. These results point to SERT as a critical regulator of glutamate homeostasis in a way that differs between the subregions investigated, the duration of cocaine exposure as well as the cellular compartment analyzed.