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-HT3 or 5-HT4 receptors. The SSRIs, paroxetine (ED50 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-HT3 receptor antagonist, ondansetron (0.1 mg/kg, IP), or the 5-HT4 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-propyl-amino)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.
CITATION STYLE
Schreiber, R., Melon, C., & De Vry, J. (1998). The role of 5-HT receptor subtypes in the anxiolytic effects of selective serotonin reuptake inhibitors in the rat ultrasonic vocalization test. Psychopharmacology, 135(4), 383–391. https://doi.org/10.1007/s002130050526
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