Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates

Abstract

Background Accumulating evidence suggests that the FDA-approved serotonin 5HT2C receptor agonist, lorcaserin (Belviq®), may be a promising candidate for the management of substance use disorders, including nicotine addiction. The present study was conducted to determine the efficacy and selectivity of acute or continuous lorcaserin treatment for decreasing the reinforcing effects of nicotine in a primate species. Methods Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2 years) responded for injections of nicotine (0.32–100 µg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement during daily 100-min sessions. When responding was stable, lorcaserin was administered either as an acute pretreatment (0.1–1.0 mg/kg, IM) or by continuous infusion (0.1 mg/kg/hr, SC for 3–5 days). Daily activity patterns were also monitored immediately following experimental sessions. Results Results indicate that acute lorcaserin pretreatment produced significant and dose-dependent decreases in nicotine-maintained responding across a >100-fold range of self-administered nicotine doses. Continuous lorcaserin treatment decreased intake of 10 µg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding was only moderately decreased in 3 of 4 subjects after acute administration and unaffected in all subjects during continuous treatment. Daily activity also was significantly decreased—to ≤50% of control values—following experimental sessions in which acute lorcaserin was administered. Conclusions These data indicate that lorcaserin reduces IV self-administration of nicotine at a dose that decreases motoric activity but less consistently disrupts food-maintained responding. Further research into lorcaserin’s potential utility for the management of nicotine dependence is warranted.

Lorcaserin decreases the reinforcing effects of heroin, but not food, in rhesus monkeys

“…The present study shows that acute pretreatment with lorcaserin produces dose-related and nearly complete attenuation of self-administration across a 10–30-fold range of IV heroin doses, with little effect on food-maintained responding. These data are consistent with previous studies showing flattening of dose-response curves for stimulants such as nicotine (Jacobs et al, 2017), cocaine (Collins et al 2016), and methampetamine (Gerak et al, 2016) by lorcaserin in nonhuman primates. The present study extends this previous work to the abused opioid, heroin.…”

“…Studies in both rodents and nonhuman primates have demonstrated that cocaine- or amphetamine-induced elevations in extracellular dopamine levels in striatum can be decreased or further increased by, respectively, serotonin 2C receptor agonists (Manvich et al, 2012; Berro et al, 2017) and antagonists (Manvich et al, 2012; Zayara et al, 2011; Navailles et al, 2007; Filip and Cunningham, 2002). As well, we and others have reported that lorcaserin (Belviq ® ), an FDA-approved weight loss medication, like other serotonin 2C receptor agonists (e.g., Ro 60–0175), markedly reduces self-administration of stimulant drugs such as cocaine or amphetamines (Harvey-Lewis et al, 2016; Collins et al, 2016; Gerak et al, 2016; Gannon et al, 2018; though see Banks et al, 2017) and nicotine (Levin et al, 2011; Fletcher et al, 2012; Jacobs et al, 2017). Further, these effects occur at doses that do not appreciably alter other ongoing behaviors, suggesting that serotonin 2C receptor agonists, and in particular, lorcaserin, may be viable candidates as medication for the management of stimulant use disorder.…”

“…The effects of acute pretreatment with lorcaserin was studied in test sessions that were routinely conducted on the second day of the double alternation schedule, if control rates and patterns of self-administration behavior were evident in the previous session. Lorcaserin was administered 15-min prior to the onset of experimental sessions; doses were selected on the basis of previous studies to evaluate those that produced moderate (0.32 mg/kg, IM) and marked (1.0 mg/kg, IM) decreases in nicotine self-administration in rhesus monkeys (Jacobs et al, 2017). The effects of each dose of lorcaserin during sessions in which saline and a range of heroin doses (0.32 – 32 μg/kg/inj, IV) were available for IV self-administration were studied in an irregular order across subjects.…”

Effects of chronic treatment with bupropion on self-administration of nicotine + cocaine mixtures in nonhuman primates.

“…To prevent carry-over effects, successive treatment doses were separated by periods of continuous saline treatment that continued daily until drug- and food-maintained responding returned to stable baseline levels. Daily activity was recorded using a three-way accelerometer (Fitbit Zip) attached to the subjects’ jacket (Jacobs, Barkin, Kohut, Bergman, & Kohut, 2017).…”

Reinforcing and Stimulant-Like Effects of Methamphetamine Isomers in Rhesus Macaques

“…Daily activity was measured using a commercially available 3-way accelerometer (FitBit Zip, FitBit, San Francisco, CA) attached to the back of each subjects' nylon jacket. The accelerometer used has been shown to produce reliable activity data in human studies (Imboden et al, 2017) and was used here to measure total daily activity counts as we have previously reported from macaque subjects (Jacobs et al, 2017). Data was downloaded at least twice weekly through Bluetooth technology.…”