NR2B subunit-specific NMDA antagonist Ro25-6981 inhibits the expression of conditioned fear: A comparison with the NMDA antagonist MK-801 and fluoxetine

J. Haller, Rita Nagy, M. Tóth, Katalin Gyimesine Pelczer, E. Mikics

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19 Citations (Scopus)

Abstract

N-methyl-D-asparate (NMDA)-mediated glutamatergic neurotransmission is strongly involved in the development of trauma-induced behavioral dysfunctions, and indirect evidence suggests that NR2B subunit-expressing NMDA receptors are primarily involved in this process. Earlier studies showed that NR2B blockers inhibit the acquisition of conditioned fear, a frequently used model of post-traumatic stress disorder, but their effects on the expression of conditioned fear was poorly studied. We investigated here the effects of the selective serotonin reuptake blocker, fluoxetine, the NMDA blocker, MK-801, and the NR2B subunit blocker, Ro25-6981 on the expression of conditioned fear. Rats received 10 foot shocks administered over 5 min and were tested 24 h later in the shocking context. Treatments were administered 1 h before testing. Shocks dramatically increased freezing and reduced exploration. MK-801 and Ro25-6981 significantly ameliorated both changes. The effects of fluoxetine were less pronounced. In the open field, MK-801 increased locomotion, ataxia, and stereotypy (effects typical of NMDA blockade). Neither fluoxetine nor Ro25-6981 affected locomotion in the open field. Thus, the NR2B-specific NMDA blockade preserved the beneficial effects of general NMDA antagonists on the expression of conditioned fear but did not produce the locomotor side-effects typical of the latter. These findings warrant further studies on the effects of NR2B antagonists in models of post-traumatic stress disorder.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalBehavioural Pharmacology
Volume22
Issue number2
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Dizocilpine Maleate
Fluoxetine
Fear
Locomotion
Post-Traumatic Stress Disorders
Shock
Ataxia
Synaptic Transmission
Freezing
Serotonin
Ro 25-6981
Wounds and Injuries

Keywords

  • conditioned fear
  • N-methyl-D-asparate
  • NR2B subunit
  • post-traumatic stress disorder
  • rat
  • Ro25-6981

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

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title = "NR2B subunit-specific NMDA antagonist Ro25-6981 inhibits the expression of conditioned fear: A comparison with the NMDA antagonist MK-801 and fluoxetine",
abstract = "N-methyl-D-asparate (NMDA)-mediated glutamatergic neurotransmission is strongly involved in the development of trauma-induced behavioral dysfunctions, and indirect evidence suggests that NR2B subunit-expressing NMDA receptors are primarily involved in this process. Earlier studies showed that NR2B blockers inhibit the acquisition of conditioned fear, a frequently used model of post-traumatic stress disorder, but their effects on the expression of conditioned fear was poorly studied. We investigated here the effects of the selective serotonin reuptake blocker, fluoxetine, the NMDA blocker, MK-801, and the NR2B subunit blocker, Ro25-6981 on the expression of conditioned fear. Rats received 10 foot shocks administered over 5 min and were tested 24 h later in the shocking context. Treatments were administered 1 h before testing. Shocks dramatically increased freezing and reduced exploration. MK-801 and Ro25-6981 significantly ameliorated both changes. The effects of fluoxetine were less pronounced. In the open field, MK-801 increased locomotion, ataxia, and stereotypy (effects typical of NMDA blockade). Neither fluoxetine nor Ro25-6981 affected locomotion in the open field. Thus, the NR2B-specific NMDA blockade preserved the beneficial effects of general NMDA antagonists on the expression of conditioned fear but did not produce the locomotor side-effects typical of the latter. These findings warrant further studies on the effects of NR2B antagonists in models of post-traumatic stress disorder.",
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