Tags

Type your tag names separated by a space and hit enter

Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study.
Synapse. 2001 Jun 15; 40(4):275-81.S

Abstract

In this study, we determined the activity of midbrain dopamine (DA) neurons in male albino rats following the intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotide (aODN) against the mRNA for the NR1 subunit of the NMDA receptor. In addition, the effect of aODN on the specific binding of the NMDA receptor ligand [(3)H]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 administered into the right ventricle of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding studies indicated that aODN significantly reduced the density of [(3)H]MK-801 binding by an average of 20-30% in several forebrain regions, including the anterior cingulate cortex, caudate putamen, and nucleus accumbens. However, [(3)H]MK-801 binding was not significantly 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 and SNC DA neurons compared to saline- of sODN-treated animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons was not significantly altered. However, for spontaneously active VTA DA neurons, the administration of aODN significantly decreased the percent events in bursts, number of bursts, and percentage of DA neurons exhibiting a bursting pattern compared to saline- and sODN-treated animals, i.e., neurons show less bursting activity. The present results suggest that subchronic aODN treatment against the mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA receptor number and can result in an altered activity of spontaneously active VTA DA neurons in anesthetized rats.

Authors+Show Affiliations

Department of Neuropsychiatry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. tajiri@ms.toyama-mpu.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11309843

Citation

Tajiri, K, et al. "Intracerebroventricular Administration of NMDA-R1 Antisense Oligodeoxynucleotide Significantly Alters the Activity of Ventral Tegmental Area Dopamine Neurons: an Electrophysiological Study." Synapse (New York, N.Y.), vol. 40, no. 4, 2001, pp. 275-81.
Tajiri K, Emori K, Murata M, et al. Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study. Synapse. 2001;40(4):275-81.
Tajiri, K., Emori, K., Murata, M., Tanaka, K., Suzuki, M., Uehara, T., Sumiyoshi, T., Ashby, C. R., & Kurachi, M. (2001). Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study. Synapse (New York, N.Y.), 40(4), 275-81.
Tajiri K, et al. Intracerebroventricular Administration of NMDA-R1 Antisense Oligodeoxynucleotide Significantly Alters the Activity of Ventral Tegmental Area Dopamine Neurons: an Electrophysiological Study. Synapse. 2001 Jun 15;40(4):275-81. PubMed PMID: 11309843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study. AU - Tajiri,K, AU - Emori,K, AU - Murata,M, AU - Tanaka,K, AU - Suzuki,M, AU - Uehara,T, AU - Sumiyoshi,T, AU - Ashby,C R,Jr AU - Kurachi,M, PY - 2001/4/20/pubmed PY - 2001/7/28/medline PY - 2001/4/20/entrez SP - 275 EP - 81 JF - Synapse (New York, N.Y.) JO - Synapse VL - 40 IS - 4 N2 - In this study, we determined the activity of midbrain dopamine (DA) neurons in male albino rats following the intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotide (aODN) against the mRNA for the NR1 subunit of the NMDA receptor. In addition, the effect of aODN on the specific binding of the NMDA receptor ligand [(3)H]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 administered into the right ventricle of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding studies indicated that aODN significantly reduced the density of [(3)H]MK-801 binding by an average of 20-30% in several forebrain regions, including the anterior cingulate cortex, caudate putamen, and nucleus accumbens. However, [(3)H]MK-801 binding was not significantly 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 and SNC DA neurons compared to saline- of sODN-treated animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons was not significantly altered. However, for spontaneously active VTA DA neurons, the administration of aODN significantly decreased the percent events in bursts, number of bursts, and percentage of DA neurons exhibiting a bursting pattern compared to saline- and sODN-treated animals, i.e., neurons show less bursting activity. The present results suggest that subchronic aODN treatment against the mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA receptor number and can result in an altered activity of spontaneously active VTA DA neurons in anesthetized rats. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/11309843/Intracerebroventricular_administration_of_NMDA_R1_antisense_oligodeoxynucleotide_significantly_alters_the_activity_of_ventral_tegmental_area_dopamine_neurons:_an_electrophysiological_study_ L2 - https://doi.org/10.1002/syn.1050 DB - PRIME DP - Unbound Medicine ER -