The selective serotonin (5-HT)1A receptor ligand, S15535, displays anxiolytic-like effects in the social interaction and Vogel models and suppresses dialysate levels of 5-HT in the dorsal hippocampus of freely-moving rats. A comparison with other anxiolytic agents

A Dekeyne, M Brocco, A Adhumeau, A Gobert, M J Millan
Psychopharmacology 2000, 152 (1): 55-66

RATIONALE: The benzodioxane, S15535, possesses low intrinsic activity and marked selectivity at 5-HT1A receptors, hippocampal populations of which are implicated in anxious states.

OBJECTIVE: Herein, we examined its potential anxiolytic actions in relation to its influence upon extracellular levels of 5-HT in the dorsal hippocampus of freely-moving rats. Its effects were compared with those of other anxiolytic agents: the 5-HT1A agonists, buspirone and 8-hydroxy-2-(di-n-propylamino)-tetralin HBr (8-OH-DPAT), the 5-HT2C antagonist, SB206,553 and the benzodiazepine, diazepam.

METHODS: Potential anxiolytic actions were evaluated in the Vogel conflict paradigm (increase in punished responses) and the social interaction (SI) test (increase in active SI) in rats. Extracellular levels of 5-HT were determined by microdialysis.

RESULTS: In analogy to diazepam. S15535 increased punished responses in the Vogel test. This action was dose dependently expressed over a broad (16-fold) dose range. Buspirone and 8-OH-DPAT were likewise active, but yielded highly biphasic dose-response curves. SB206,553 was dose dependently active in this model. In the SI test, S15535 similarly mimicked the anxiolytic-like effect of diazepam and was active over a broad dose range. Buspirone and 8-OH-DPAT again showed biphasic dose-response curves, as did SB206,553. In both the Vogel and SI tests, the anxiolytic-like effects of S15535 were abolished by the selective 5-HT1A receptor antagonist, WAY100,635, which was inactive alone. S15535 exerted its anxiolytic-like effects with a more pronounced separation to motor-disruptive doses than the other drugs. Finally, S15535 suppressed dialysate levels of 5-HT in the dorsal hippocampus, an action abolished by WAY100,635. Buspirone, 8-OH-DPAT and diazepam, but not SB206,553, also reduced 5-HT levels.

CONCLUSION: Likely reflecting its distinctive ability to selectively and preferentially activate pre- versus postsynaptic 5-HT1A receptors, S15535 suppresses hippocampal 5-HT release and displays marked anxiolytic-like effects over a broad dose range in the relative absence of motor perturbation.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"