Lorcaserin, a 5-HT_2C Agonist, Decreases Nicotine Self-Administration in Female Rats

Abstract

Lorcaserin, a selective 5-hydroxytryptamine 2C (5-HT 2C ) agonist, has been shown to facilitate weight loss in obese populations. It was assessed for its efficacy in reducing nicotine self-administration in young adult female Sprague-Dawley rats. The effect of short-term doses (subcutaneous) on nicotine selfadministration (0.03 mg/kg per infusion) with a fixed ratio 1 schedule was assessed in 3-h sessions. Short-term lorcaserin doses (0.3125-20 mg/kg) were administered in a counterbalanced order. Significant reduction of nicotine self-administration was achieved with all of the short-term doses in this range. Tests of lorcaserin on locomotor activity detected prominent sedative effects at doses greater than 1.25 mg/kg with more modest transient effects seen at 0.625 to 1.25 mg/kg. Longterm effects of lorcaserin on locomotor activity were tested with repeated injections with 0.625 mg/kg lorcaserin 10 times over 2 weeks. This low lorcaserin dose did not cause an overall change in locomotor activity relative to that of saline-injected controls. Long-term lorcaserin (0.625 mg/kg) significantly reduced nicotine self-administration over a 2-week period of repeated injections. Long-term lorcaserin at this same dose had no significant effects on food self-administration over the same 2-week period of repeated injections. These studies support development of the 5-HT 2C agonist lorcaserin to aid tobacco smoking cessation.

Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys

“…In clinical studies, lorcaserin is well tolerated and decreases food intake and body weight (Smith et al, 2009(Smith et al, , 2010Chan et al, 2013;Aronne et al, 2014) at doses that have low potential for producing heart valve disease (Weissman et al, 2013) or abuse (Shram et al, 2011), effects commonly associated with 5-HT 2B and 5-HT 2A receptor agonists, respectively (Nichols, 2004;Hutcheson et al, 2011). In addition to preclinical studies demonstrating that lorcaserin decreases food intake and body weight (Smith et al, 2008;Thomsen et al, 2008;Higgins et al, 2013b;Grottick et al, 2015), lorcaserin is also shown to decrease nicotine selfadministration and the reinstatement of responding for nicotine in rats (Levin et al, 2011;Higgins et al, 2012Higgins et al, , 2013b.…”

Tabaco y peso corporal

“…un estudio clínico reciente en fase ii demostró que la lorcaserina se asoció con una tasa mayor en el cese del tabaquismo sumado a una reducción en el peso corporal comparado con placebo 8 . Por otra parte, estudios en animales han demostrado que lorcaserina reduce la autoadministración de nicotina 9 . El uso de lorcaserina se asocia a una baja de peso promedio de 3 kg en pacientes con peso cercano a 100 kg, o una reducción en el iMC de 1,2 kg/m 2 en pacientes con iMC basal de 36 kg/ m 2 .…”

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What Has Been Investigated, and What Is in the Pipeline?

“…In preclinical studies, lorcaserin was found to decrease nicotine self-administration and nicotineenhanced responding for conditioned reinforcement in rats [266][267][268]. A recent phase 2 clinical trial found that lorcaserin was associated with a significantly higher continuous quit rate compared with placebo.…”

“…In addition, lorcaserin used alone or combination with varenlicine may be a novel agent for smoking cessation given that 5-HT systems play key roles in the action of nicotine [266].…”