Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamineneurons: An electrophysiological study

Citation
K. Tajiri et al., Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamineneurons: An electrophysiological study, SYNAPSE, 40(4), 2001, pp. 275-281
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
SYNAPSE
ISSN journal
0887-4476 → ACNP
Volume
40
Issue
4
Year of publication
2001
Pages
275 - 281
Database
ISI
SICI code
0887-4476(20010615)40:4<275:IAONAO>2.0.ZU;2-X
Abstract
In this study, we determined the activity of midbrain dopamine (DA) neurons in male albino rats following the intracerebroventricular (i.c.v.) adminis tration of antisense oligodeoxynucleotide (aODN) against the mRNA for the N R1 subunit of the NMDA receptor. In addition, the effect of aODN on the spe cific binding of the NMDA receptor ligand [H-3]MK-801 was also examined in various brain areas, including the midbrain. Antisense ODN against the NR1 mRNA, the corresponding sense ODN (sODN) or saline was continuously adminis tered into the right ventricle of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding studies indicated that aODN significant ly reduced the density of [H-3]MK-801 binding by an average of 20-30% in se veral forebrain regions, including the anterior cingulate cortex, caudate p utamen, and nucleus accumbens. However, [H-3]MK-801 binding was not signifi cantly altered in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNC). Subsequently, using the technique of extracellular single- unit recording, the number, as well as the firing pattern, of spontaneously active DA neurons was determined in the VTA and SNC. The administration of aODN did not significantly alter the number of spontaneously active VTA an d SNC DA neurons compared to saline- of sODN-treated animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons was not significa ntly altered. However, for spontaneously active VTA DA neurons, the adminis tration of aODN significantly decreased the percent events in bursts, numbe r of bursts, and percentage of DA neurons exhibiting a bursting pattern com pared to saline- and sODN-treated animals, i.e., neurons show less bursting activity. The present results suggest that subchronic aODN treatment again st the mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA recep tor number and can result in an altered activity of spontaneously active VT A DA neurons in anesthetized rats. Synapse 40: 275-281, 20101. (C) 2001 Wil ey-Liss, Inc.