biostudies-literatureUnknown179(14)Caffino L<h4>Background and purpose</h4>It has been well established that glutamate in the nucleus accumbens (NAc) plays a critical role in the motivation to take drugs of abuse. We have previously demonstrated that rats with ablation of the serotonin transporter (SERT^-/- rats) show increased cocaine intake reminiscent of compulsivity.<h4>Experimental approach</h4>By comparing SERT^-/- to SERT^+/+ rats, we investigated whether SERT deletion influences glutamate homeostasis under control conditions as well as after short access (ShA: 1 h per session) or long access (LgA: 6 h per session) to cocaine self-administration. Rats were killed at 24 h after the last self-administration session for ex vivo molecular analyses of the main determinants of the glutamate system, including transporters (vesicular and glial), receptors (main post-synaptic subunits of NMDA and AMPA receptors together with the metabotropic subunit mGLUR5), and scaffolding proteins (SAP102, SAP97, and GRIP) in the NAc shell (sNAc) KEY RESULTS: In cocaine-naive animals, SERT deletion was associated with changes indicative for a reduction in glutamate signalling. ShA and LgA exposure led to a further dysregulation of the glutamatergic synapse.<h4>Conclusion</h4>SERT deletion may render the glutamatergic synapses of the NAc shell more responsive to both ShA and LgA intake of cocaine.British journal of pharmacology3727-3739https://www.ebi.ac.uk/biostudies/studies/S-EPMC9310702biostudies-literatureResponsivity of serotonin transporter knockout rats to short and long access to cocaine: Modulation of the glutamate signalling in the nucleus accumbens shell.PMC9310702Mottarlini FVerheij MMMCaffino LFumagalli FTarga GHomberg JRfalseResponsivity of serotonin transporter knockout rats to short and long access to cocaine: Modulation of the glutamate signalling in the nucleus accumbens shell.<h4>Background and purpose</h4>It has been well established that glutamate in the nucleus accumbens (NAc) plays a critical role in the motivation to take drugs of abuse. We have previously demonstrated that rats with ablation of the serotonin transporter (SERT^-/- rats) show increased cocaine intake reminiscent of compulsivity.<h4>Experimental approach</h4>By comparing SERT^-/- to SERT^+/+ rats, we investigated whether SERT deletion influences glutamate homeostasis under control conditions as well as after short access (ShA: 1 h per session) or long access (LgA: 6 h per session) to cocaine self-administration. Rats were killed at 24 h after the last self-administration session for ex vivo molecular analyses of the main determinants of the glutamate system, including transporters (vesicular and glial), receptors (main post-synaptic subunits of NMDA and AMPA receptors together with the metabotropic subunit mGLUR5), and scaffolding proteins (SAP102, SAP97, and GRIP) in the NAc shell (sNAc) KEY RESULTS: In cocaine-naive animals, SERT deletion was associated with changes indicative for a reduction in glutamate signalling. ShA and LgA exposure led to a further dysregulation of the glutamatergic synapse.<h4>Conclusion</h4>SERT deletion may render the glutamatergic synapses of the NAc shell more responsive to both ShA and LgA intake of cocaine.2022-01-01T00:00:00Z2022 Jul2024-11-13T17:42:06.097Z2022-08-06T14:52:06.845ZS-EPMC93107023517448910.1111/bph.15823