Dataset Information

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

ABSTRACT: Accumulating evidence suggests that the FDA-approved serotonin 5-HT2C 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.Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2years) responded for injections of nicotine (0.32-100?g/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 (0.1-1.0mg/kg, IM) or by continuous infusion (0.1mg/kg/hr, SC for 3-5days). Daily activity patterns were also monitored immediately following experimental sessions.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?g/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.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.

SUBMITTER: Jacobs DS

PROVIDER: S-EPMC5857383 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Effects of lorcaserin (Belviq<sup>®</sup>) on nicotine- and food-maintained responding in non-human primates.

Jacobs David S DS Barkin Claire E CE Kohut Michelle R MR Bergman Jack J Kohut Stephen J SJ

Drug and alcohol dependence 20171010

<h4>Background</h4>Accumulating evidence suggests that the FDA-approved serotonin 5-HT<sub>2C</sub> receptor agonist, lorcaserin (Belviq<sup>®</sup>), 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.<h4>Methods</h4>Adult rhesus monkeys (n=4) with a his ...[more]

PMID: 29040827

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Project description:Chemotherapies of varying classes often cause neuropathy and debilitating chemotherapy-induced neuropathic pain sufficient to limit treatment and reduce quality of life for many patients battling cancer. There are currently no effective preventive or alleviative treatments for chemotherapy-induced neuropathic pain. Preclinical models have been developed to test candidate chemotherapy-induced neuropathic pain treatments; however, studies using these models rarely provide direct comparisons of effects of different chemotherapies or assess the degree to which chemotherapies produce clinically relevant signs of pain-depressed behavior. Male and female Sprague-Dawley rats received four injections of vehicle, paclitaxel, oxaliplatin, vincristine, or bortezomib on alternate days. Mechanical hypersensitivity, body weight, and food-maintained operant responding were evaluated before, during, and for up to 42 days after initiation of treatment. Morphine potency and effectiveness to reverse chemotherapy-induced effects were also evaluated. All four chemotherapies produced dose-dependent and sustained mechanical hypersensitivity in all rats. Vincristine and oxaliplatin produced transient weight loss and decreases in food-maintained operant responding in all rats, whereas paclitaxel and bortezomib produced lesser or no effect. At 4 weeks after treatment, operant responding was depressed only in paclitaxel-treated males. Morphine reversed mechanical hypersensitivity in all rats but failed to reverse paclitaxel-induced depression of operant responding in males. We conclude that chemotherapy treatments sufficient to produce sustained mechanical hypersensitivity failed to produce sustained or morphine-reversible behavioral depression in rats. Insofar as pain-related behavioral depression is a cardinal sign of chemotherapy-induced neuropathic pain in humans, these results challenge the presumption that these chemotherapy-dosing regimens are sufficient to model clinically relevant chemotherapy-induced neuropathic pain in rats.

Project description:ObjectiveTo introduce a novel technology currently under final development before regulatory approvals for the furtherment of cataract surgery, using the FemtoMatrix® laser system, and to demonstrate its safety and efficacy as compared to standard ultrasound phacoemulsification.MethodsThirty-three patients with bilateral cataracts were operated on with one eye undergoing PhotoEmulsification® treatment on the FemtoMatrix® device and the contralateral eye receiving the control procedure, i.e., standard ultrasound phacoemulsification treatment. The number of "zero-phaco" procedures (denoting that I/A alone was sufficient to aspirate the lens fragments and that no ultrasound energy was needed) was recorded and Effective Phaco Time (EPT) values were compared. The patient follow-up was 3 months.ResultsThirty-three eyes from a population with a mean cataract grade of 2.6 were treated on the FemtoMatrix®, of which 29 were "zero-phaco" (88%). All patients were operated on by a single surgeon who was a relative novice to the technology (63 patients treated prior to this study). Conversely, of the 33 fellow eyes who underwent standard ultrasound phacoemulsification, none were zero-phaco (0%) - all required varying degrees of ultrasound energy to make lens aspiration possible. The mean EPT was significantly lower in the PhotoEmulsification® laser group (0.2 ± 0.8 s) than in the phaco group (1.3 ± 1.2 s) (p < 0.0001). The safety profiles of the two procedures were comparable, with no device-related adverse events noted.ConclusionFemtoMatrix® is a promising femtosecond laser platform that, when compared to phacoemulsification, significantly decreases or eliminates EPT altogether. The system is used to perform PhotoEmulsification®, making zero-phaco cataract procedures feasible including in high-grade cataracts (>3). It enables personalized treatment by automatically measuring and adapting the laser energy required to obtain the most efficient cutting of the crystalline lens. This new technology appears to be safe and effective in cataract surgery.

Dataset Information

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

Publications

Effects of lorcaserin (Belviq<sup>®</sup>) on nicotine- and food-maintained responding in non-human primates.

Similar Datasets

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