Abstract

Human studies have consistently shown that drugs of abuse affect memory function. The psychostimulants amphetamine and the “bath salt” 3,4-methylenedioxypyrovalerone (MDPV) increase brain monoamine levels through a similar, yet not identical, mechanism of action. Findings indicate that amphetamine enhances the consolidation of memory for emotional experiences, but still MDPV effects on memory function are underinvestigated. Here, we tested the effects induced by these two drugs on generalization of fear memory and their relative neurobiological underpinnings. To this aim, we used a modified version of the classical inhibitory avoidance task, termed inhibitory avoidance discrimination task. According to such procedure, adult male Sprague–Dawley rats were first exposed to one inhibitory avoidance apparatus and, with a 1-min delay, to a second apparatus where they received an inescapable footshock. Forty-eight hours later, retention latencies were tested, in a randomized order, in the two training apparatuses as well as in a novel contextually modified apparatus to assess both strength and generalization of memory. Our results indicated that both amphetamine and MDPV induced generalization of fear memory, whereas only amphetamine enhanced memory strength. Co-administration of the β-adrenoceptor antagonist propranolol prevented the effects of both amphetamine and MDPV on the strength and generalization of memory. The dopaminergic receptor blocker cis-flupenthixol selectively reversed the amphetamine effect on memory generalization. These findings indicate that amphetamine and MDPV induce generalization of fear memory through different modulations of noradrenergic and dopaminergic neurotransmission.

Highlights

  • Drugs of abuse are characterized by rewarding effects induced by the engagement of specific pathways in the brain (McHugh and Kneeland, 2019)

  • Rats were trained on the inhibitory avoidance discrimination task and given an immediate post-training intraperitoneal injection of amphetamine, MDPV or saline

  • The present findings indicate that amphetamine and MDPV have different effects on memory strength, but both drugs increase generalization of fear memory to a novel safe context

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Summary

Introduction

Drugs of abuse are characterized by rewarding effects induced by the engagement of specific pathways in the brain (McHugh and Kneeland, 2019). A novel experimental model suitable to investigate both strength and accuracy of memory has been validated for rodents (Atucha and Roozendaal, 2015; Atucha et al, 2017): the inhibitory avoidance discrimination task This task allows to evaluate whether fear memory associated with footshock can be generalized to a novel and safe, yet similar context. The aim of the present study was to investigate whether the two psychostimulants amphetamine and MDPV affect generalization of fear memory to a novel and safe yet similar context using an inhibitory avoidance discrimination task Since both amphetamine and MDPV modulate NE and DA tone, we aimed at evaluating the involvement of the noradrenergic and dopaminergic systems in mediating the effects of amphetamine and MDPV on fear memory generalization

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