Chronic dietary magnesium-L-threonate speeds extinction and reduces spontaneous recovery of a conditioned taste aversion

Abstract

Elevation of brain magnesium enhances synaptic plasticity and extinction of conditioned fear memories. This experiment examined the generalizability of this phenomenon by studying the effects of a novel magnesium compound, magnesium-L-threonate (MgT), on conditioned taste aversion (CTA) extinction and spontaneous recovery (SR). Adult male Sprague-Dawley rats were maintained on a 23-hour water deprivation cycle and acquired a CTA following the taste of a CS [0.3% saccharin + 16mg/ml MgT (SAC+MgT)] paired with a US [81 mg/kg (i.p.) Lithium Chloride (LiCl)]. Following CTA acquisition, rats drank a water + MgT solution for up to 1 hour/day over the next 31 days. For 14 additional days, some animals continued water + MgT treatment, but others drank water only to allow MgT to be eliminated from the body. We then employed 2 different extinction paradigms: (1) CS-Only (CSO), in which SAC was presented, every-other day, or (2) Explicitly Unpaired (EU), in which both SAC and LiCl were presented, but on alternate days. EU extinction procedures have been shown to speed CTA extinction and reduce spontaneous recovery of the aversion. Throughout extinction, half of the rats in each group continued to drink MgT (now in SAC or supplemental water+MgT solution), whereas the other half drank SAC only/water only until SAC drinking reached ≥ 90% of baseline (asymptotic extinction). Rats receiving MgT just before/during extinction drank less SAC on the first day of extinction suggesting that they had retained a stronger CTA. MgT enhanced the rate of extinction. Furthermore, the MgT-treated rats showed a relatively modest SR of the CTA 30 days later – indicating that the extinction procedure was more effective for these animals. Our data suggest that long-term dietary MgT may enhance the consolidation/retention of a CTA, speed extinction, and inhibit SR of this learned aversion.

Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

“…Although these effects may be mediated by Zn2+ modulation of NMDAR signaling, other actions cannot be excluded (e.g., see discussion on HDAC inhibition in Section 4.10: Epigenetics ). The same is true for another NMDAR-modulating ion, Mg2+, which has also been shown to facilitate extinction when globally enhanced in the brain ( Abumaria et al, 2011 ; Mickley et al, 2013 ).…”

Magnesium efflux from Drosophila Kenyon cells is critical for normal and diet-enhanced long-term memory

“…Prior studies reported that feeding rats with food containing a high concentration of Mg 2+ -enhanced their learning and memory capability ( Slutsky et al, 2010 ; Landfield and Morgan, 1984 ; Abumaria et al, 2011 ; Mickley et al, 2013 ; Abumaria et al, 2013 ). We therefore tested whether similar effects exist in flies by feeding them with food containing a high concentration of Mg 2+ before training.…”

“…Mg 2+ enhanced their learning and memory capability (Slutsky et al, 2010;Landfield and Morgan, 1984;Abumaria et al, 2011;Mickley et al, 2013;Abumaria et al, 2013).…”

“…Perhaps surprisingly, increasing brain Mg 2+ through diet can enhance neuronal plasticity and memory performance of young and aged rodents, measured in a variety of behavioral tasks ( Slutsky et al, 2010 ; Landfield and Morgan, 1984 ; Mickley et al, 2013 ; Abumaria et al, 2013 ). In addition, elevated Mg 2+ reduced cognitive deficits in a mouse model of Alzheimer’s disease ( Li et al, 2013 ) and enhanced the extinction of fear memories ( Abumaria et al, 2011 ).…”

Effect of Magnesium Oxide Nanoparticles on Atropine-Induced Memory Impairment in Adult Male Mice

“…Atropine is an anticholinergic drug that is a cholinergic muscarinic receptor antagonist. Clinical and experimental evidence suggests that the central or systemic administration of anticholinergic drugs such as atropine leads to an impaired memory (4). In one experiment, mice treated with atropine resulted in both decreased levels of hippocampal acetylcholine and spatial memory impairment (5).…”