Role of ventral hippocampal NMDA receptors in anxiolytic-like effect of morphine

Physiol Behav. 2010 Dec 2;101(5):608-13. doi: 10.1016/j.physbeh.2010.09.013. Epub 2010 Sep 24.


The possible role of ventral hippocampal N-methyl-d-aspartate (NMDA) receptors on morphine-induced anxiolytic-like behavior in an elevated plus maze (EPM) task was investigated in the present study. Adult male mice (7 per group) with cannulas aimed at the ventral hippocampus (VH) received NMDA or a competitive NMDA receptor antagonist D-AP5 with or without morphine and 30min later were subjected to an EPM task. Intraperitoneal injection (i.p.) of morphine (3-9mg/kg) increased the percentage of open arm time (%OAT) and open arm entries (%OAE), which suggested an anxiolytic-like effect. Intra-VH microinjection of NMDA (0.5-1μg/mouse) with an ineffective dose of morphine (3mg/kg, i.p.) significantly increased %OAT and %OAE. However, microinjections of the same doses of NMDA into the VH in the absence of morphine had no effect on %OAT and %OAE. Intra-VH microinjection of D-AP5 (0.5-2μg/mouse) decreased the anxiolytic-like effect of morphine, while intra-VH microinjection of the same doses of D-AP5 alone increased %OAT and %OAE, which indicated an anxiolytic response. Furthermore, intra-VH microinjection of D-AP5 reversed the effect of NMDA response to the administration of a lower morphine dose as seen in the EPM task. It should be noted that intra-VH microinjection of D-AP5 plus NMDA, 5min before morphine increased locomotor activity, while other treatments had no effect on this parameter. The results suggest that VH-NMDA receptors participate in the mediation of morphine-induced anxiolytic-like behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Analysis of Variance
  • Animals
  • Anxiety / drug therapy*
  • Anxiety / physiopathology
  • Behavior, Animal / drug effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Mice
  • Microinjections
  • Morphine / pharmacology*
  • Morphine / therapeutic use*
  • Motor Activity / drug effects
  • N-Methylaspartate / pharmacology
  • Narcotics / pharmacology
  • Narcotics / therapeutic use
  • Receptors, N-Methyl-D-Aspartate / physiology*


  • Excitatory Amino Acid Antagonists
  • Narcotics
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • 2-Amino-5-phosphonovalerate
  • Morphine