5-HT1A and 5-HT1C/1D receptor agonists produce reciprocal effects on male sexual behavior of rhesus monkeys

Pomeratz, Steven M.; Hepner, Bert C.; Wertz, Joan M.

doi:10.1016/0014-2999(93)90179-l

Cited by 47 publications

(7 citation statements)

References 19 publications

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“…The time course for yawning induced by 3.2 mg/kg lorcaserin closely matched plasma drug concentrations after administration of this dose, including the lack of behavioral effect and disappearance of lorcaserin in blood 24 hours after administration. These findings are consistent with a role for 5-HT 2C receptors in mediating the induction of yawning by drugs acting on 5-HT mechanisms (Pomerantz et al, 1993;Collins and Eguibar, 2010). In addition to yawning, larger doses of lorcaserin also decreased spontaneous activity and food-maintained responding in all monkeys and produced oral-facial stereotypies (i.e., abnormal tongue movements) in a subset of monkeys.…”

Section: Discussionsupporting

confidence: 84%

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

Collins

Gerak

Javors

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Cocaine abuse and obesity are serious public health problems, and studies suggest that both dopamine and serotonin systems are involved in regulating the consumption of drugs and food. Lorcaserin has serotonin (5-HT) 2C receptor agonist actions, is approved by the U.S. Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intragastric administration) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration) in rhesus monkeys. Administered acutely, lorcaserin dosedependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30-60 minutes of administration and began to dissipate by 240 minutes, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine dose-response curve to the right and down in two of three monkeys. When administered acutely, lorcaserin dosedependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment period. Together, these results show that lorcaserin attenuates the discriminative stimulus effects of cocaine after acute administration and the reinforcing effects of cocaine after acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse.

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Section: Discussionsupporting

confidence: 84%

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

Collins

Gerak

Javors

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…For example, pharmacokinetic interactions between lorcaserin and cocaine could impact the effectiveness of lorcaserin or result in dangerous blood levels of cocaine; however, plasma concentrations of lorcaserin and cocaine were not changed when the two were administered together (Collins et al, 2016). Also, yawning, which is mediated by agonist actions at 5-HT 2C receptors (Pomerantz et al, 1993;Collins and Eguibar, 2010), occurred after administration of 3.2 mg/kg with a time course that closely followed changes in plasma drug concentrations obtained after administration of the same dose (Collins et al, 2016). In the current study, yawning was noted in one monkey receiving 10 mg/kg lorcaserin and in all three monkeys receiving 17.8 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys

Gerak

Collins

France

2016

J Pharmacol Exp Ther

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Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin [5-hydroxytryptamine (5-HT)] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1-1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32-100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10-17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals.

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“…The effect of antidepressants on SF appears to be influenced by the extent to which each drug effects serotonin, norepinephrine, and dopamine reuptake inhibition; prolactin release; and inhibition of NO synthetase (20,21). Among commonly prescribed antidepressants, SSRIs are most likely to be associated with impaired SF (22,23).…”

Section: Discussionmentioning

confidence: 99%

Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder

et al. 2006

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5-HT1A and 5-HT1C/1D receptor agonists produce reciprocal effects on male sexual behavior of rhesus monkeys

Cited by 47 publications

References 19 publications

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

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

Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys

Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder

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