Dorsal hippocampal opioidergic system modulates anxiety-like behaviors in adult male Wistar rats

Psychiatry Clin Neurosci. 2010 Dec;64(6):634-41. doi: 10.1111/j.1440-1819.2010.02143.x. Epub 2010 Oct 28.


Aims: In the present study, we investigated the possible influence of the opioidergic system of the dorsal hippocampus on anxiety-like behaviors.

Methods: Elevated plus-maze, which is one of the methods used for testing anxiety, was used in the present study. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After 1 week of recovery, the effects of intra-CA1 administration of morphine (0.25, 0.5, 1 and 2 µg/rat; 1 µl/rat; 0.5 µl/in each side), naloxone (2, 4, 6 and 8 µg/rat), enkephalin (1, 2, 5 and 10 µg/rat) and naltrindole (0.25, 0.5, 1 and 2 µg/rat) on percentage open arm time (%OAT) and percentage open arm entries (%OAE) were determined.

Results: Bilateral administration of morphine into CA1 decreases %OAT and %OAE, indicating an anxiogenic-like effect. Intra-CA1 injection of naloxone, an opioid receptor antagonist, increased both %OAT and %OAE, parameters of anxiolytic-like behavior. Bilateral administration of δ-opioid receptor agonist, [D-Pen(2,5) ]-enkephalin acetate hydrate into the CA1, induced an anxiolytic-like effect. Furthermore, intra-CA1 injection of δ-opioid receptor antagonist, naltrindole hydrochloride, increased anxiety-related behaviors.

Conclusions: The results of the present study demonstrate that activation of μ-opioid receptors in this area produce an anxiogenic response while activation of δ-opioid receptors produces an anxiolytic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Anxiety / physiopathology*
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiopathology*
  • Disease Models, Animal
  • Enkephalin, D-Penicillamine (2,5)- / pharmacology
  • Male
  • Maze Learning / drug effects
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, delta / agonists
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / physiology*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / physiology*


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Naloxone
  • Naltrexone
  • Morphine
  • Enkephalin, D-Penicillamine (2,5)-
  • naltrindole