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
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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
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↵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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