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Research ArticleArticle

Full Agonistic Properties of Bay x 3702 on Presynaptic and Postsynaptic 5-HT1A Receptors Electrophysiological Studies in the Rat Hippocampus and Dorsal Raphe.

Jianming Dong, Claude de Montigny and Pierre Blier
Journal of Pharmacology and Experimental Therapeutics September 1998, 286 (3) 1239-1247;
Jianming Dong
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Claude de Montigny
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Pierre Blier
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Abstract

The present studies evaluated the effects of acute and long-term administration of the 5-HT1A agonist BAY x 3702 on the responsiveness of dorsal raphe 5-HT neurons and of dorsal hippocampus CA3 pyramidal neurons. BAY x 3702 potently reduced the firing activity of 5-HT neurons and of CA3 pyramidal neurons when applied by microiontophoresis and this inhibitory effect of BAY x 3702 was fully antagonized by low intravenous doses of the 5-HT1A antagonist WAY 100635. Concurrent microiontophoretic application of BAY x 3702 did not antagonize the suppressant effect of 5-HT on firing activity of 5-HT and CA3 pyramidal neurons. Sustained administration of BAY x 3702 for 2 days (1 and 1.25 mg/kg/day using osmotic minipumps implanted subcutaneously) markedly decreased the firing rate of dorsal raphe 5-HT neurons. This was followed by a full recovery to normal after only 7 days of treatment. The postsynaptic 5-HT1A receptors in the hippocampus, contrary to the presynaptic 5-HT1A receptors, were not desensitized after a 14-day treatment. In conclusion, BAY x 3702 acted as a full and potent agonist both at somatodendritic 5-HT1A autoreceptors and at postsynaptic 5-HT1A receptors. Long-term administration of BAY x 3702 resulted in a desensitization of the somatodendritic 5-HT1A autoreceptors, but in an unaltered responsiveness of 5-HT1A receptors on pyramidal neurons. These results suggest that sustained administration of BAY x 3702 enhances neurotransmission at postsynaptic 5-HT1Areceptors.

Footnotes

  • Send reprint requests to: Dr. Jianming Dong, Neurobiological Psychiatry Unit, McGill University, 1033 Pine Avenue West, Montréal, Québec, Canada H3A 1A1. E-mail:midd{at}musica.mcgill.ca

  • ↵1 This work was supported in part by the Medical Research Council of Canada (MRC) grants (MT-11014 and MA-6444 to P.B. and C. de M., respectively) and Bayer, Germany. P.B. was in receipt of a Scientist Award from the MRC.

    • Received January 28, 1998.
    • Accepted April 21, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 286, Issue 3
1 Sep 1998
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Research ArticleArticle

Full Agonistic Properties of Bay x 3702 on Presynaptic and Postsynaptic 5-HT1A Receptors Electrophysiological Studies in the Rat Hippocampus and Dorsal Raphe.

Jianming Dong, Claude de Montigny and Pierre Blier
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1239-1247;

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Research ArticleArticle

Full Agonistic Properties of Bay x 3702 on Presynaptic and Postsynaptic 5-HT1A Receptors Electrophysiological Studies in the Rat Hippocampus and Dorsal Raphe.

Jianming Dong, Claude de Montigny and Pierre Blier
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1239-1247;
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