Prenatal morphine alters the synaptic complex of postsynaptic density 95 with N-methyl-d-aspartate receptor subunit in hippocampal CA1 subregion of rat offspring leading to long-term cognitive deficits

Neuroscience ◽  
2009 ◽  
Vol 158 (4) ◽  
pp. 1326-1337 ◽  
Author(s):  
C.S. Lin ◽  
P.L. Tao ◽  
Y.J. Jong ◽  
W.F. Chen ◽  
C.H. Yang ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Postsynaptic Density ◽  
Receptor Subunit ◽  
Synaptic Complex ◽  
Rat Offspring ◽  
Aspartate Receptor ◽  
Hippocampal Ca1

scholarly journals Long-Lasting Alterations in Gene Expression of Postsynaptic Density 95 and Inotropic Glutamatergic Receptor Subunit in the Mesocorticolimbic System of Rat Offspring Born to Morphine-Addicted Mothers

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Pei-Ling Wu ◽  
Yung-Ning Yang ◽  
Jau-Ling Suen ◽  
Yu-Chen S. H. Yang ◽  
Chun-Hwa Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nmda Receptor ◽  
Glutamate Receptor ◽  
Ampa Receptor ◽  
Prenatal Exposure ◽  
Molecular Mechanisms ◽  
Postsynaptic Density ◽  
Receptor Subunit ◽  
Rat Offspring ◽  
Ampa Receptor Subunit

Prenatal exposure to morphine causes altered glutamatergic neurotransmission, which plays an important pathophysiological role for neurobiological basis of opiate-mediated behaviors in such offspring. However, it is still not clear whether such alteration involves gene expression of ionotropic glutamate receptor subunits. In this study, we further studied whether prenatal morphine exposure resulted in long-term changes in the gene expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and postsynaptic density 95 in the mesocorticolimbic area (an essential integration circuitry for drug craving behavior), nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC), of rat offspring from morphine-addicted mothers. Experimental results showed that prenatal morphine exposure led to a persistent downregulation of gene expression in the AMPA and NMDA receptor subunit, with a differential manner of decreased magnitudes, at the age of postnatal days 14 (P14) and P30. However, in PFC, the gene expression of the AMPA receptor subunit was not synchronized in observed rat offspring subjected to prenatal morphine exposure. An upregulation of gene expression in the AMPA receptor subunit 3 (GluR3) was persistently observed at P14 and P30. Furthermore, the gene expressions of PSD-95 in NAc, VTA, and PFC were all decreased concurrently. Collectively, the results suggest that prenatal exposure to morphine may initiate molecular mechanisms leading to a long-lasting, differential alteration in gene expression of the inotropic glutamate receptor subunit and PSD-95 in the mesocorticolimbic circuitry in rat offspring. This study raises a possibility in which differential changes in gene expression with a long-lasting manner may play a role for the development of nearly permanent changes in opiate-mediated behaviors, at least in part for the neurobiological pathogenesis in offspring.

scholarly journals (2S,6S)- and (2R,6R)-hydroxynorketamine inhibit the induction of NMDA receptor-dependent LTP at hippocampal CA1 synapses in mice

2020 ◽  
Vol 4 ◽  
pp. 239821282095784
Author(s):  
Heather Kang ◽  
Pojeong Park ◽  
Muchun Han ◽  
Patrick Tidball ◽  
John Georgiou ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Long Term Potentiation ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Mouse Hippocampus ◽  
Site Of Action ◽  
A Site

The ketamine metabolite (2 R,6 R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ( R,S)-ketamine with the (2 S,6 S)- and (2 R,6 R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor–dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1–10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2 S,6 S)-hydroxynorketamine. At a concentration of 10 μM, (2 R,6 R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor–mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.

scholarly journals Uncovering long-term existence of a silent short-term memory trace

2021 ◽  
Author(s):  
Maha E. Wally ◽  
Masanori Nomoto ◽  
Kareem Abdou ◽  
Kaoru Inokuchi
Keyword(s):  
Protein Synthesis ◽  
Memory Trace ◽  
Short Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Aspartate Receptor ◽  
Hippocampal Ca1 ◽  
Term Functions

Active recall of short-term memory (STM) is known to last for a few hours, but whether STM has long-term functions is unknown. Here we show that, STM can be optogenetically retrieved at a time point during which natural recall is not possible, uncovering the long-term existence of a silent STM engram. Moreover, re-training within 3 days led to natural long-term recall, indicating facilitated consolidation. Calcium imaging revealed hippocampal CA1 reactivations of the STM trace during post-learning sleep. Inhibiting offline CA1 activity, N-methyl-D-aspartate receptor activity, or protein synthesis after first exposure to the STM-forming event impaired the future re-exposure-facilitated consolidation, which highlights a role of protein synthesis and sleep in storing a silent STM trace. These results provide evidence that STM is not completely lost within hours and demonstrates a possible two-step STM consolidation, first storage as a silent engram, then transformation into an active state by recurrence within 3 days.

Permanent deficits in brain functions caused by long-term ketamine treatment in mice

2010 ◽  
Vol 30 (9) ◽  
pp. 1287-1296 ◽  
Author(s):  
L Sun ◽  
WP Lam ◽  
YW Wong ◽  
LH Lam ◽  
HC Tang ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Cognitive Deficits ◽  
Long Term Effects ◽  
Post Dose ◽  
Significant Deterioration ◽  
Competitive Antagonist ◽  
Brain Functions ◽  
Aspartate Receptor

Ketamine, an injectable anesthetic, is also a popular recreational drug used by young adults worldwide. Ketamine is a non-competitive antagonist of N-methyl-d-aspartate receptor, which plays important roles in synaptic plasticity and neuronal learning. Most previous studies have examined the immediate and short-term effects of ketamine, which include learning and cognitive deficits plus impairment of working memory, whereas little is known about the long-term effects of repeated ketamine injections of common or usual recreational doses. Therefore, we aimed to evaluate the deficits in brain functions with behavioral tests, including wire hang, hot plate and water maze tests, plus examine prefrontal cortex apoptotic markers, including Bax, Bcl-2 and caspase-3, in mice treated with 6 months of daily ketamine administration. In our study, following 6 months of ketamine injection, mice showed significant deterioration in neuromuscular strength and nociception 4 hours post-dose, but learning and working memory were not affected nor was there significant apoptosis in the prefrontal cortex. Our research revealed the important clinical finding that long-term ketamine abuse with usual recreational doses can detrimentally affect neuromuscular strength and nociception as part of measurable, stable and persistent deficits in brain function.

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