Latency to paroxetine‐induced anxiolysis in the rat is reduced by co‐administration of the 5‐HT 1A receptor antagonist WAY100635

Latency to paroxetine‐induced anxiolysis in the rat is reduced by co‐administration of the... We report here the use of rat high‐light social interaction to model the temporal anxiolytic/antidepressant effects of SSRIs seen in the clinic. Compared to vehicle controls, 21, but not 14, days of paroxetine treatment (3 mg kg−1, p.o., daily) produced a marked increase in rat social interaction (Vehicle=71.3±7.3 s; Paroxetine=116.7±14.7 s; P<0.01) with no concurrent effect on locomotor activity, consistent with anxiolysis. To assess whether concurrent 5‐HT1A receptor blockade reduces the time to onset of anxiolysis seen with paroxetine alone (21 days), rats were implanted with osmotic minipumps to continuously infuse the 5‐HT1A receptor antagonist WAY100635 (1 mg kg−1 day−1, s.c., 7 days) alone or in combination with paroxetine (3 mg kg−1, p.o., daily, 7 days), prior to anxiety testing. Paroxetine (Veh/Par=61.9±7.9 s) or WAY100635 (WAY/Veh=71.6±4.7 s) alone, had no effect on social interaction time compared to vehicle treated controls (Veh/Veh=76.4±4.9 s), whilst coadministration of WAY100635 with paroxetine, produced a marked elevation in social interaction (WAY/Par=149.3±16.8 s; P<0.01) relative to all other groups with no concurrent change in locomotor activity. In contrast, acute administration of WAY100635 (0.03 mg kg−1, s.c.) with paroxetine (3 mg kg−1, p.o.) did not alter any behavioural measure, suggesting that the anxiolysis induced by the combination after 7 days is attributable to a CNS adaptive response. This data demonstrates that coadministration of a 5‐HT1A receptor antagonist with paroxetine markedly reduces the latency to anxiolysis, in the rat. This study supports the use of the rat social interaction test to further delineate adaptive changes in the CNS responsible for the anxiolytic/antidepressant action of SSRIs seen in humans. British Journal of Pharmacology (2000) 130, 1713–1719; doi:10.1038/sj.bjp.0703496 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Latency to paroxetine‐induced anxiolysis in the rat is reduced by co‐administration of the 5‐HT 1A receptor antagonist WAY100635

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Publisher
Wiley
Copyright
2000 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0703496
pmid
10928979
Publisher site
See Article on Publisher Site

Abstract

We report here the use of rat high‐light social interaction to model the temporal anxiolytic/antidepressant effects of SSRIs seen in the clinic. Compared to vehicle controls, 21, but not 14, days of paroxetine treatment (3 mg kg−1, p.o., daily) produced a marked increase in rat social interaction (Vehicle=71.3±7.3 s; Paroxetine=116.7±14.7 s; P<0.01) with no concurrent effect on locomotor activity, consistent with anxiolysis. To assess whether concurrent 5‐HT1A receptor blockade reduces the time to onset of anxiolysis seen with paroxetine alone (21 days), rats were implanted with osmotic minipumps to continuously infuse the 5‐HT1A receptor antagonist WAY100635 (1 mg kg−1 day−1, s.c., 7 days) alone or in combination with paroxetine (3 mg kg−1, p.o., daily, 7 days), prior to anxiety testing. Paroxetine (Veh/Par=61.9±7.9 s) or WAY100635 (WAY/Veh=71.6±4.7 s) alone, had no effect on social interaction time compared to vehicle treated controls (Veh/Veh=76.4±4.9 s), whilst coadministration of WAY100635 with paroxetine, produced a marked elevation in social interaction (WAY/Par=149.3±16.8 s; P<0.01) relative to all other groups with no concurrent change in locomotor activity. In contrast, acute administration of WAY100635 (0.03 mg kg−1, s.c.) with paroxetine (3 mg kg−1, p.o.) did not alter any behavioural measure, suggesting that the anxiolysis induced by the combination after 7 days is attributable to a CNS adaptive response. This data demonstrates that coadministration of a 5‐HT1A receptor antagonist with paroxetine markedly reduces the latency to anxiolysis, in the rat. This study supports the use of the rat social interaction test to further delineate adaptive changes in the CNS responsible for the anxiolytic/antidepressant action of SSRIs seen in humans. British Journal of Pharmacology (2000) 130, 1713–1719; doi:10.1038/sj.bjp.0703496

Journal

British Journal of PharmacologyWiley

Published: Aug 1, 2000

References

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