In serotonin transporter knockout (SERT ) and wild-type control (SERT ) rats we assessed the locomotor response to acute amphetamine (AMPH) and intravenous AMPH self-administration under short access (ShA: 1-hr daily sessions) and long access (LgA: 6-hr daily sessions) conditions. 24 hrs after AMPH self-administration we analysed the expression of glutamate system components in the nucleus accumbens shell and core.
We found that SERT animals displayed an increased AMPH-induced locomotor response and increased AMPH self-administration under LgA, but not ShA conditions. Further, we observed changes in the vesicular and glial glutamate transporters, NMDA and AMPA receptor subunits and their respective postsynaptic scaffolding proteins as function of serotonin transporter genotype and AMPH exposure (baseline, ShA and LgA), specifically in the nucleus accumbens shell.
We demonstrate that SERT gene deletion increases the psychomotor and reinforcing effects of AMPH, and that the latter is potentially mediated, at least in part, by homeostatic changes in the glutamatergic synapse of the nucleus accumbens shell and/or core.
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