Pentylenetetrazol and Morphine Interaction in a State-dependent Memory Model: Role of CREB Signaling

Abstract

Introduction: State-dependent (STD) memory is a process, in which the learned information can be optimally retrieved only when the subject is in the state similar to the encoding phase. This phenomenon has been widely studied with morphine. Several studies have reported that Pentylenetetrazole (PTZ) impairs memory in experimental animal models. Due to certain mechanistic interactions between morphine and PTZ, it is hypothesized that PTZ may interfere with the morphine-STD. The cyclic adenosine monophosphate Response Element-Binding (CREB) is considered as the main downstream marker for long-term memory. This study was designed to determine the possible interaction between PTZ and morphine STD and the presumable changes in CREB mRNA. Methods: In an Inhibitory Avoidance (IA) model, posttraining morphine (2.5, 5, and 7.5 mg/ kg-i.p.) was used. The pre-test morphine was evaluated for morphine-induced STD memory. Moreover, the effect of a pre-test PTZ (60 mg/kg-i.p.) was studied along with morphine STD. Locomotion testing was carried out using open-field. Eventually, using real-time-PCR, the CREB mRNA changes in the hippocampus were evaluated. Results: Posttraining MOR (7.5 mg/kg-i.p.) impaired IA memory (P<0.001). The pre-test injection of similar doses of morphine recovered the morphine-induced memory impairment (P<0.001). The pre-test PTZ impaired the IA memory recall (P<0.001); however, the pre-test PTZ along with morphine STD potentiated the morphine-induced STD (P<0.001). Alterations in CREB mRNA were observed in all groups. No difference was seen in the locomotor activity. Conclusion: Presumably, the certain interactive effect of PTZ on morphine-induced STD is mediated through gamma-aminobutyric acid and opioid systems via CREB signaling.

Investigating the Co-administration of Ghrelin and Nicotine into the Medial Septum and Its Influencing on Morphine Amnestic Effect

“…Consistent with prior results (Adedayo et al, 2018;Ghasemzadeh and Rezayof, 2017;Tavassoli et al, 2020), in the present study, morphine administration cause to passive avoidance memory consolidation impairment. Previously, it has been shown that morphine-induced memory impairment results from changes in CAMKII/CREB and also BDNF/cFos signaling pathways Rezayof, 2016, 2018).…”

“…Passive avoidance learning is a hippocampus-dependent simple task which widely use in memory studies in rodents (Atucha and Roozendaal et al, 2015). According to previous studies, acute exposure to morphine could affect various aspects of memory formation in avoidance learning (Adedayo et al, 2018;Ghasemzadeh and Rezayof, 2017;Tavassoli et al, 2020). Our previous studies showed that injection of ghrelin into the hippocampus or anterior port of ventral tegmental area (VTA) improved morphine-induced memory impairment and this improvement is associated with the acetylcholine nicotinic receptor activity (Nazari-Serenjeh et al, 2019;Yadegay et al, 2020).…”