Responsivity of serotonin transporter knockout rats to short and long access to cocaine: modulation of the glutamate signaling in the nucleus accumbens shell
Articolo
Data di Pubblicazione:
2022
Citazione:
Responsivity of serotonin transporter knockout rats to short and long access to cocaine: modulation of the glutamate signaling in the nucleus accumbens shell / L. Caffino, F. Mottarlini, G. Targa, M.M.M. Verheij, F. Fumagalli, J.R. Homberg. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 1476-5381. - 179:14(2022 Jul), pp. 3727-3739. [10.1111/bph.15823]
Abstract:
Background and Purpose 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. Experimental Approach 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. Conclusion SERT deletion may render the glutamatergic synapses of the NAc shell more responsive to both ShA and LgA intake of cocaine.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
cocaine self-administration; glutamate; nucleus accumbens; serotonin transporter;
Elenco autori:
L. Caffino, F. Mottarlini, G. Targa, M.M.M. Verheij, F. Fumagalli, J.R. Homberg
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