Cocaine use disorder is a serious, chronic and relapsing disease of the nervous system, for which effective treatments do not yet exist. Recently, the role of the N-methyl-d-aspartate (NMDA) receptor subunit GluN2B has been highlighted in cocaine abstinence followed by extinction training. Since the GluN2B subunit is stabilized at synaptic level by the interaction with its scaffolding protein PSD95, in this study we aimed at investigating efficacy of Tat-NR2B9c peptide, a PSD95 inhibitor, which disrupts the interaction of PSD95 with GluN2B, in the attenuation of cocaine seeking-behavior or cue-induced reinstatement. We found that Tat-NR2B9c, administered intravenously, attenuated the reinstatement of active lever presses induced by a priming dose of cocaine or by drug-associated conditioned stimuli. At the same time, the GluN2B/PSD95 complex levels were decreased in the ventral hippocampus of rats that previously self-administered cocaine injected with Tat-NR2B9c during cocaine- or cue-induced reinstatement. In conclusion, we here provide the first evidence showing that the disruption of the GluN2B/PSD95 complexes during cocaine abstinence followed by extinction training may represent a useful strategy to reduce reinstatement of cocaine-seeking behavior.

Intravenous administration of Tat-NR2B9c peptide, a PSD95 inhibitor, attenuates reinstatement of cocaine-seeking behavior in rats / I. Smaga, K. Wydra, K. Witek, P. Surówka, A. Suder, R. Pieniążek, L. Caffino, F. Fumagalli, M. Sanak, M. Filip. - In: BEHAVIOURAL BRAIN RESEARCH. - ISSN 0166-4328. - 416(2022 Jan), pp. 113537.1-113537.5. [10.1016/j.bbr.2021.113537]

Intravenous administration of Tat-NR2B9c peptide, a PSD95 inhibitor, attenuates reinstatement of cocaine-seeking behavior in rats

Caffino, Lucia;Fumagalli, Fabio;
2022-01

Abstract

Cocaine use disorder is a serious, chronic and relapsing disease of the nervous system, for which effective treatments do not yet exist. Recently, the role of the N-methyl-d-aspartate (NMDA) receptor subunit GluN2B has been highlighted in cocaine abstinence followed by extinction training. Since the GluN2B subunit is stabilized at synaptic level by the interaction with its scaffolding protein PSD95, in this study we aimed at investigating efficacy of Tat-NR2B9c peptide, a PSD95 inhibitor, which disrupts the interaction of PSD95 with GluN2B, in the attenuation of cocaine seeking-behavior or cue-induced reinstatement. We found that Tat-NR2B9c, administered intravenously, attenuated the reinstatement of active lever presses induced by a priming dose of cocaine or by drug-associated conditioned stimuli. At the same time, the GluN2B/PSD95 complex levels were decreased in the ventral hippocampus of rats that previously self-administered cocaine injected with Tat-NR2B9c during cocaine- or cue-induced reinstatement. In conclusion, we here provide the first evidence showing that the disruption of the GluN2B/PSD95 complexes during cocaine abstinence followed by extinction training may represent a useful strategy to reduce reinstatement of cocaine-seeking behavior.
cocaine self-administration; extinction training; GluN2B; PSD95; Tat-NR2B9c
Settore BIO/14 - Farmacologia
17-ago-2021
BEHAVIOURAL BRAIN RESEARCH
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0166432821004253-main.pdf

accesso aperto

1.1 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/863242
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact