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2.
Pharmacol Biochem Behav ; 201: 173111, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33444602

RESUMEN

This study was designed to examine the effects of intra- nucleus accumbens (NAc) of BDNF receptor antagonist ANA-12 on the acquisition and expression and intra- medial-prefrontal cortex (mPFC) of ANA-12 on the extinction and reinstatement of morphine-induced conditioned place preference (CPP) and also BDNF levels and apoptotic neurons in the NAc and mPFC of rats. In this study, adult male Wistar rats (200-250 g) were used. Two separate cannulas were inserted bilaterally into the NAc and/or mPFC. ANA-12 (3 µg/0.5 µl/side) was injected into the NAc and/or mPFC to evaluate the rewarding effects of morphine using a CPP paradigm. Then, the levels of BDNF and apoptotic in the NAc and mPFC were assessed at the end of each treatment phase using ELISA and TUNEL methods, respectively. All of vehicle-treated rats following morphine CPP showed the increase of BDNF levels and apoptotic neurons in the NAc and mPFC. ANA-12 significantly attenuated the acquisition and expression of morphine-induced CPP, BDNF levels and apoptotic neurons in the NAc during the acquisition, but not the expression phase. Also, ANA-12 significantly facilitated the extinction, but no effect on reinstatement of morphine CPP, and decreased BDNF levels and apoptotic neurons in the mPFC during the extinction, but not the reinstatement. We conclude that blocking TrkB with ANA-12 showed therapeutic effects on morphine-associated reward memory and neuronal death in the NAc and mPFC induced by morphine CPP. Thus, the BDNF-TrkB signaling may be important in the acquisition, expression, extinction, but not the reinstatement of morphine CPP.


Asunto(s)
Apoptosis/efectos de los fármacos , Azepinas/administración & dosificación , Benzamidas/administración & dosificación , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Memoria/efectos de los fármacos , Microinyecciones/métodos , Morfina/administración & dosificación , Núcleo Accumbens/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Receptor trkB/antagonistas & inhibidores , Recompensa , Transducción de Señal/efectos de los fármacos , Animales , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Operante/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Núcleo Accumbens/metabolismo , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar
3.
Neurosci Lett ; 668: 7-12, 2018 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-29294331

RESUMEN

This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and psychological dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert-Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats.


Asunto(s)
Ansiedad/tratamiento farmacológico , Azepinas/farmacología , Benzamidas/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Dependencia de Morfina/tratamiento farmacológico , Actividad Motora/efectos de los fármacos , Núcleo Accumbens , Inhibidores de Proteínas Quinasas/farmacología , Receptor trkB/antagonistas & inhibidores , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Área Tegmental Ventral , Animales , Azepinas/administración & dosificación , Conducta Animal/efectos de los fármacos , Benzamidas/administración & dosificación , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Masculino , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/metabolismo
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