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

Author(s):Show less -

Milanesi, Laura Hautrive ^[1] ; Rossato, Domenika Rubert ^[1] ; Oliveira da Rosa, Jessica Leandra ^[1] ; D'avila, Livia Ferraz ^[1] ; Metz, Vinicia Garzella ^[1] ; Wolf, Jessica Fernanda ^[2] ; Reis, Vanessa B. ^[3] ; de Andrade, Diego F. ^[4] ; Jank, Louise ^[4] ; Beck, Ruy C. R. ^[5] ; da Silva, Cristiane de B. ^[2] ; Burger, Marilise E. ^{[1, 6]}

Affiliation

^[1] Univ Fed Santa Maria UFSM, Programa Posgrad Farmacol, Santa Maria, RS - Brazil

^[2] Univ Fed Santa Maria UFSM, Programa Posgrad Ciencias Farmaceut, Santa Maria, RS - Brazil

^[3] Univ Fed Santa Maria UFSM, Curso Farm, Santa Maria, RS - Brazil

^[4] Minist Agr Pecuaria & Abastecimento MAPA, Lab Fed Def Agr LFDA, Secretaria Def Agr SDA, Santa Maria, RS - Brazil

^[5] Univ Fed Rio Grande do Sul UFRGS, Programa Posgrad Ciencias Farmaceut, Porto Alegre, RS - Brazil

^[6] Univ Fed Santa Maria UFSM, Dept Fisiol & Farmacol, Santa Maria, RS - Brazil

• Document type: Journal article
• Source: NEUROCHEMISTRY INTERNATIONAL; v. 150, NOV 2021.
• Web of Science Citations: 0

Abstract

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 nonencapsulated 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. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants