Topiramate-chitosan nanoparticles prevent morphine reinstatement with no memory impairment: Dopaminergic and glutamatergic molecular aspects in rats.

Autor: Milanesi LH; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil. Electronic address: laura-milanesi@hotmail.com., Rossato DR; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., Oliveira da Rosa JL; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., D'avila LF; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., Metz VG; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., Wolf JF; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., Reis VB; Curso de Farmácia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., de Andrade DF; Laboratório Federal de Defesa Agropecuária (LFDA), Secretaria de Defesa Agropecuária (SDA), Ministério da Agricultura,Pecuária e Abastecimento (MAPA), RS, Brazil., Jank L; Laboratório Federal de Defesa Agropecuária (LFDA), Secretaria de Defesa Agropecuária (SDA), Ministério da Agricultura,Pecuária e Abastecimento (MAPA), RS, Brazil., Beck RCR; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., da Silva CB; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil., Burger ME; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil; Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2021 Nov; Vol. 150, pp. 105157. Date of Electronic Publication: 2021 Aug 12.
DOI: 10.1016/j.neuint.2021.105157
Abstrakt: Besides their clinical application, chronic misuse of opioids has often been associated to drug addiction due to their addictive properties, underlying neuroadaptations of AMPA glutamate-receptor-dependent synaptic plasticity. Topiramate (TPM), an AMPAR antagonist, has been used to treat psychostimulants addiction, despite its harmful effects on memory. This study aimed to evaluate the effects of a novel topiramate nanosystem on molecular changes related to morphine reinstatement. Rats were previously exposed to morphine in conditioned place preference (CPP) paradigm and treated with topiramate-chitosan nanoparticles (TPM-CS-NP) or non-encapsulated topiramate in solution (S-TPM) during CPP extinction; following memory performance evaluation, they were re-exposed to morphine reinstatement. While morphine-CPP extinction was comparable among all experimental groups, TPM-CS-NP treatment prevented morphine reinstatement, preserving memory performance, which was impaired by both morphine-conditioning and S-TPM treatment. In the NAc, morphine increased D1R, D2R, D3R, DAT, GluA1 and MOR immunoreactivity. It also increased D1R, DAT, GluA1 and MOR in the dorsal hippocampus. TPM-CS-NP treatment decreased D1R, D3R and GluA1 and increased DAT in the NAc, decreasing GluA1 and increasing D2 and DAT in the dorsal hippocampus. Taken together, we may infer that TPM-CS-NP treatment was able to prevent the morphine reinstatement without memory impairment. Therefore, TPM-CS-NP may be considered an innovative therapeutic tool due to its property to prevent opioid reinstatement because it acts modifying both dopaminergic and glutamatergic neurotransmission, which are commonly related to morphine addiction.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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