Electrophysiological evidence for rapid 5-HT1A autoreceptor inhibition by vilazodone, a 5-HT1A receptor partial agonist and 5-HT reuptake inhibitor

Abstract This study examined the effect of vilazodone, a combined serotonin (5-HT) reuptake inhibitor and 5-HT 1A receptor partial agonist, paroxetine and fluoxetine on the sensitivity of 5-HT 1A autoreceptors of serotonergic dorsal raphe nucleus neurons in rats. These effects were assessed by determining the intravenous dose of (±)-8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) required to suppress the basal firing rate of these neurons by 50% (ID 50 ) in anesthetized rats using in vivo electrophysiology. 5-HT uptake inhibition was determined by the ability of the compounds to reverse (±)- p -chloroamphetamine (PCA)-induced rat hypothalamic 5-HT depletion ex vivo . Acute vilazodone administration (0.63 and 2.1 µmol/kg, s.c.), compared with vehicle, significantly increased (2–3-fold) the ID 50 of 8-OH-DPAT at 4 h, but not 24 h after administration. Subchronic administration (3 days) significantly increased the ID 50 value at 4 h (3–4-fold) and at 24 h (~2-fold). In contrast, paroxetine and fluoxetine at doses that were supramaximal for 5-HT uptake inhibition did not significantly alter the ID 50 value of 8-OH-DPAT after acute or subchronic administration. Vilazodone antagonized the action of PCA 3.5 h and 5 h after a single dose (ID 50 1.49 and 0.46 µmol/kg, s.c., respectively), but was inactive 18 h post-administration, corroborating the electrophysiological results at 24 h following acute administration. The results are consistent with the concept of rapid and, following repeated treatment, prolonged inhibition of 5-HT 1A autoreceptors by vilazodone. This effect could occur by either direct interaction with, or desensitization of, these receptors, an effect which cannot be ascribed to vilazodone's 5-HT reuptake inhibiting properties

A Proposed High-Power UV Industrial Demonstration Laser at CEBAF

The Laser Processing Consortium, a collaboration of industries, universities, and the Continuous Electron Beam Accelerator Facility (CEBAF) in Newport News, Virginia, has proposed building a demonstration industrial processing laser for surface treatment and micro-machining. The laser is a free-electron laser (FEL) with average power output exceeding 1 kW in the ultraviolet (UV). The design calls for a novel driver accelerator that recovers most of the energy of the exhaust electron beam to produce laser light with good wall-plug efficiency. The laser and accelerator design use technologies that are scalable to much higher power. The authors will describe the critical design issues in the laser such as the stability, power handling, and losses of the optical resonator, and the quality, power, and reliability of the electron beam. They will also describe the calculated laser performance. Finally progress to date on accelerator development and resonator modeling will be reported

Proposed high-power UV industrial demonstration laser at CEBAF

The Laser Processing Consortium, a collaboration of industries, universities, and the Continuous Electron Beam Accelerator Facility (CEBAF) in Newport News, Virginia, has proposed building a demonstration industrial processing laser for surface treatment and micro-machining. The laser is a free-electron laser (FEL) with average power output exceeding 1 kW in the ultraviolet (UV). The design calls for a novel driver accelerator that recovers most of the energy of the exhaust electron beam to produce laser light with good wall-plug efficiency. The laser and accelerator design use technologies that are scalable to much higher power. The authors will describe the critical design issues in the laser such as the stability, power handling, and losses of the optical resonator, and the quality, power, and reliability of the electron beam. They will also describe the calculated laser performance. Finally progress to date on accelerator development and resonator modeling will be reported

Electrophysiological evidence for rapid 5-HT1A autoreceptor inhibition by vilazodone, a 5-HT1A receptor partial agonist and 5-HT reuptake inhibitor

AbstractThis study examined the effect of vilazodone, a combined serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist, paroxetine and fluoxetine on the sensitivity of 5-HT1A autoreceptors of serotonergic dorsal raphe nucleus neurons in rats. These effects were assessed by determining the intravenous dose of (±)-8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) required to suppress the basal firing rate of these neurons by 50% (ID50) in anesthetized rats using in vivo electrophysiology. 5-HT uptake inhibition was determined by the ability of the compounds to reverse (±)-p-chloroamphetamine (PCA)-induced rat hypothalamic 5-HT depletion ex vivo. Acute vilazodone administration (0.63 and 2.1µmol/kg, s.c.), compared with vehicle, significantly increased (2–3-fold) the ID50 of 8-OH-DPAT at 4h, but not 24h after administration. Subchronic administration (3 days) significantly increased the ID50 value at 4h (3–4-fold) and at 24h (~2-fold). In contrast, paroxetine and fluoxetine at doses that were supramaximal for 5-HT uptake inhibition did not significantly alter the ID50 value of 8-OH-DPAT after acute or subchronic administration. Vilazodone antagonized the action of PCA 3.5h and 5h after a single dose (ID50 1.49 and 0.46µmol/kg, s.c., respectively), but was inactive 18h post-administration, corroborating the electrophysiological results at 24h following acute administration. The results are consistent with the concept of rapid and, following repeated treatment, prolonged inhibition of 5-HT1A autoreceptors by vilazodone. This effect could occur by either direct interaction with, or desensitization of, these receptors, an effect which cannot be ascribed to vilazodone's 5-HT reuptake inhibiting properties