Long access to cocaine self-administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats
Articolo
Data di Pubblicazione:
2021
Citazione:
Long access to cocaine self-administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats / L. Caffino, F. Mottarlini, G. Targa, M.M.M. Verheij, J. Homberg, F. Fumagalli. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - (2021). [Epub ahead of print] [10.1111/bph.15496]
Abstract:
Background and Purpose: It is well established that the nucleus accumbens and glutamate play a critical role in the motivation to take drugs of abuse. We have previously demonstrated that rats with ablation of the serotonin (5-HT) transporter (SERT−/− rats) show increased cocaine intake reminiscent of compulsivity. Experimental Approach: By comparing SERT−/− to SERT+/+ rats, we set out to explore whether SERT deletion influences glutamate neurotransmission under control conditions as well as after short access (1 h/session) or long access (6 h/session) to cocaine self-administration. Key Results: Rats were killed at 24 h after the final self-administration session for ex vivo molecular analyses of the glutamate system (vesicular and glial transporters, post-synaptic subunits of NMDA and AMPA receptors and their related scaffolding proteins). Such analyses were undertaken in the nucleus accumbens core. In cocaine-naïve animals, SERT deletion evoked widespread abnormalities in markers of glutamatergic neurotransmission that, overall, indicate a reduction of glutamate signalling. These results suggest that 5-HT is pivotal for the maintenance of accumbal glutamate homeostasis. We also found that SERT deletion altered glutamate homeostasis mainly after long access, but not short access, to cocaine. Conclusion and Implications: Our findings reveal that SERT deletion may sensitize the glutamatergic synapses of the nucleus accumbens core to the long access but not short access, 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, J. Homberg, F. Fumagalli
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