5-HT1A receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5-HT neurons in the median raphe nucleus

Eur Neuropsychopharmacol. 2008 Apr;18(4):286-94. doi: 10.1016/j.euroneuro.2007.07.007. Epub 2007 Aug 28.

Abstract

We evaluated the involvement of dorsal hippocampus (DH) 5-HT1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-maze test of anxiety. The results showed that intra-DH injection of the 5-HT1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT1A antagonist WAY-100635 was ineffective. In the elevated T-maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra-MRN administration of the excitatory amino acid kainic acid, which non-selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra-MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Pre-administration of WAY-100635 into the DH blocked the behavioral effect of intra-MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Anxiety / psychology*
  • Behavior, Animal / drug effects
  • Electric Stimulation
  • Excitatory Amino Acid Agonists / pharmacology
  • Hippocampus / metabolism*
  • Hippocampus / physiology
  • Kainic Acid / pharmacology
  • Male
  • Microinjections
  • Motor Activity / drug effects
  • Neurons / physiology*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Excitatory Amino Acid Agonists
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Kainic Acid