Abstract
Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0.5, 1.0, 2.5, 5.0, 10, or 20 mg/kg i.p.) as well as the interaction between scopolamine and verapamil on memory consolidation in the step-through passive avoidance task, in Wistar rats. Our results showed that verapamil (1.0 and 2.5 mg/kg) administered immediately after the acquisition task significantly increased the latency of the passive avoidance response, on the 48 h retested trial, improving memory consolidation. On the other hand, verapamil in a dose of 5 mg/kg, that per se does not affect memory consolidation, significantly reversed the memory consolidation improvement induced by scopolamine (1 mg/kg, i.p., administered immediately after verapamil treatment) but did not change the passive avoidance response in rats treated by an ineffective dose of scopolamine (30 mg/kg). In conclusion, the present data suggest that (1) the post-training administration of verapamil, dose-dependently, improves the passive avoidance response; (2) verapamil, in ineffective dose, abolished the improvement of memory consolidation effect of scopolamine; and (3) exists interaction between cholinergic muscarinic receptors and calcium homeostasis-related mechanisms in the consolidation of emotional memory.
Highlights
The influx of Ca2++ through the L-type voltage-gated calcium channels (LVGCCs) promotes several molecular processes that are engaged in learning and memory (Singewald et al, 2015; BasOrth et al, 2016; Sachser et al, 2016; Michalak and Biala, 2017; Wiera et al, 2017)
The aim of the present study was to evaluate the effect of verapamil as well as the interaction between cholinergic muscarinic receptors and calcium homeostasis on memory consolidation, in the passive avoidance task, in rats
In animals treated with verapamil at the doses of 1 and 2.5 mg/kg, the step-through latency on the 48 h retention trial was significantly higher in comparison to the groups treated with saline (p = 0.037 and p = 0.012, respectively), verapamil in the dose of 0.5 (p = 0.029 and p = 0.009, respectively) and 20 mg/kg (p = 0.028 and p = 0.009, respectively)
Summary
The influx of Ca2++ through the L-type voltage-gated calcium channels (LVGCCs) promotes several molecular processes that are engaged in learning and memory (Singewald et al, 2015; BasOrth et al, 2016; Sachser et al, 2016; Michalak and Biala, 2017; Wiera et al, 2017). Acute verapamil treatment improves acquisition in passive avoidance and elevated plus maze tasks (Biala et al, 2013; Michalak and Biala, 2017) while does not affect acquisition in conditioned avoidance response, T-maze, and linear maze tasks (Malekar et al, 1999; Quartermain and Garcia de Soria, 2001; Quartermain et al, 2001). It has been found that acute verapamil treatment impairs familiarity discrimination and perirhinal plasticity, in rats (Seoane et al, 2009). Rats exposed for prolonged period to a high dose of verapamil (50 mg/kg) impaired passive avoidance learning, while lower doses applied either acutely or chronically did not affect passive avoidance performance (Lazarova-Bakarova et al, 1997; Lashgari et al, 2006). The chronic verapamil treatment in rats does not modify acquisition but prejudices retention of the radial maze task (Borroni et al, 2000; Woodside et al, 2004)
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