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We evaluated whether the anxiolytic effects of selective serotonin reuptake inhibitors (SSRIs) in the rat ultrasonic vocalization (USV) test are preferentially mediated by (indirect) activation of 5-HT 1A , 5-HT 1B/1D , 5-HT 2A , 5-HT 3 or 5-HT 4 receptors. The SSRIs, paroxetine (ED 50 in mg/kg, IP: 6.9), citalopram (6.5), fluvoxamine (11.7) and fluoxetine (>30), dose dependently reduced shock-induced USV. The effects of paroxetine (3.0 mg/kg, IP) were not blocked by the selective 5-HT 1A receptor antagonist, WAY-100635 (3.0 mg/kg, IP), the 5-HT 1B/1D receptor antagonist, GR 127935 (30 mg/kg, IP), the nonselective 5-HT 2A receptor antagonists, ritanserin (3.0 mg/kg, IP) and ketanserin (1.0 mg/kg, IP), the 5-HT 3 receptor antagonist, ondansetron (0.1 mg/kg, IP), or the 5-HT 4 receptor antagonist, GR 125487D (3.0 mg/kg, SC). In contrast, the selective 5-HT 2A receptor antagonist, MDL 100,907 (0.1 mg/kg, IP), completely prevented the paroxetine-induced reduction of USV. Under similar conditions, WAY-100635 blocked the anxiolytic-like effects of the selective 5-HT 1A receptor agonist, 8-OH-DPAT ((±)-8-hydroxy-2-(di- n -propylamino)tetralin, 1.0 mg/kg, IP), and ritanserin, ketanserin, and MDL 100,907 blocked the anxiolytic-like effects of the mixed 5-HT 2A/2C receptor agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, 3.0 mg/kg, IP). WAY-100635 (1.0 mg/kg, IP) in combination with ritanserin (3.0 mg/kg, IP), but not ondansetron (0.1 mg/kg, IP), GR 125487D (3.0 mg/ kg, SC), or GR 127935 (30 mg/kg, IP), attenuated the USV reducing effects of paroxetine. Although the results suggest that selective stimulation of 5-HT 1A and 5-HT 2A receptors produces a decrease of USV, we postulate that only 5-HT 2A receptors play a pivotal role in the effects of SSRIs in this model of anxiety.
Psychopharmacology – Springer Journals
Published: Feb 1, 1998
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