Related Experiment Videos
[3H]MK-801 binding sites in neonate rat brain
A M Morin1, H Hattori, C G Wasterlain
1Neurology Research Laboratory, V.A. Medical Center, Sepulveda, CA 91343.
Insights
Neonatal rat brains exhibit N-methyl-D-aspartate-type glutamate receptors with MK-801 binding sites present from birth. These receptors are functionally coupled by 7 days postnatally, showing distinct regional expression patterns compared to adults.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pharmacology
Background:
- N-methyl-D-aspartate (NMDA) receptors are crucial ionotropic glutamate receptors involved in synaptic plasticity and neurotransmission.
- MK-801 is a non-competitive antagonist that binds to the NMDA receptor-associated ion channel.
- Understanding the developmental expression and function of NMDA receptors is vital for comprehending brain development and neurological disorders.
Purpose of the Study:
- To investigate the presence and characteristics of [3H]MK-801 binding sites in the neonate rat brain.
- To compare the regional distribution and functional coupling of NMDA receptors in neonatal versus adult rats.
- To determine the developmental timeline for the functional maturation of NMDA receptor-associated MK-801 binding sites.
Main Methods:
- Radioligand binding assays using [3H]MK-801 to quantify binding sites in brain homogenates.
- Regional analysis of binding site concentration in hippocampus, cortex, and brainstem.
- Pharmacological characterization of binding, including stimulation by glutamate/glycine and blockade by phencyclidine/Mg2+.
Main Results:
- [3H]MK-801 binding sites are detectable in the neonate rat brain as early as postnatal day 3.
- Immature hippocampus and cortex show significantly lower binding site concentrations (approximately 1/6th) compared to adults.
- The brainstem exhibits a higher concentration of binding sites (twice adult levels) in neonates.
- [3H]MK-801 binding is modulated by glutamate, glycine, phencyclidine, and Mg2+ in 7-day-old neonates, mirroring adult responses.
Conclusions:
- NMDA receptor-associated MK-801 binding sites are present and pharmacologically functional in the early postnatal rat brain.
- Distinct developmental trajectories exist for NMDA receptor expression across different brain regions.
- Functional coupling of the NMDA receptor and MK-801 binding site is established by 7 days postnatally.
Abstract:
[3H]MK-801 binding sites are present in neonate rat brain as early as 3 days after birth. Immature hippocampus and cortex contain approximately one sixth the concentration of binding sites of the adult, while brainstem concentration is twice as high as that of adult. [3H]MK-801 binding is stimulated by glutamate and glycine and blocked by phencyclidine and Mg2+ both in 7-day-old neonate and adult, indicating that as early as 7 days postnatally, the N-methyl-D-aspartate-type glutamate receptor and MK-801 binding site are functionally coupled.