Opioid mechanisms are involved in the disruption of arcaine-induced amnesia by context pre-exposure

Abstract

Previous exposure to the training context disrupts glutamatergic N-methyl-d-aspartate receptor (NMDAr) antagonist-induced amnesia, indicating that novelty is necessary for such an amnestic effect. While there are reports that novelty-related release of opioids cause amnesia, no study has addressed whether the amnestic effect of NMDAr antagonists involve opioid mechanisms. In this study we investigated whether pharmacological manipulation of the opioid system immediately after context pre-exposure alters the amnestic effect of arcaine, a NMDAr antagonist. Adult male Wistar rats were habituated (pre-exposed) to a fear conditioning training apparatus or to a different context (open field). Immediately after pre-exposure, animals were injected with saline or naloxone (0.5 mg/kg, i.p.) or anti-beta-endorphin antibody (1:500, i.c.v.). Forty eight hours after pre-exposure session, all animals were subjected to fear conditioning acquisition protocol and saline or arcaine (30 mg/kg, i.p.) was administered immediately after training. Testing was carried out 24 h later, and freezing responses due to re-exposure to the training apparatus were recorded. Pre-exposure to the training apparatus prevented the impairment of memory induced by post-training arcaine. Administration of naloxone or anti-beta-endorphin antibody, immediately after pre-exposure to the training apparatus, reinstated the amnesic effect of post-training arcaine. The results suggest that endogenous opioid mechanisms are involved in the pre-exposure-induced loss of the amnestic effect of arcaine.

Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and Disease

“…Arcaine (a potent antagonist for the PA binding site on the NMDAr) at 0.002–0.2 nmol had either no effect or prevented Spd-associated consolidation during stepdown and inhibitory avoidance tasks. Spd (0.02–2 nmol) generally improved fear conditioning acquisition and consolidation whereas arcaine (0.0002–0.02 nmol or 10–30 mg/kg) treatment impaired this acquisition (Rubin et al, 2004 ; Camera et al, 2007 ; Da Rosa et al, 2012 ; Signor et al, 2014 ; Guerra and Rubin, 2016 and references therein). PAs also modify reconsolidation and extinction of fear conditioning and step-down avoidance, but the observed effects evaluated by different investigators were variable.…”

Spermine reverses lipopolysaccharide-induced memory deficit in mice

“…Numerous reports have indicated that polyamines improve memory in several tasks and attenuate memory deficits induced by different amnesic agents [ 32 - 41 ]. In fact, agonists and antagonists of the polyamine binding site at the NMDA receptor respectively facilitate and impair memory in various tasks [ 33 , 34 , 36 , 39 , 40 , 42 , 43 ], and the sequential activation of protein kinase C (PKC) and PKA/CREB (protein kinase A/cAMP response element-binding protein) pathways in the hippocampus has been implicated in the promnesic effect of polyamines [ 44 , 45 ]. However, it has recently been described that interruption of the NMDA receptor modulation by polyamines reverses Aβ 25–35 -induced memory impairment in mice in a novel object recognition task [ 46 ], suggesting that the role of polyamines in memory may vary in physiological and pathological conditions.…”