title: Repeated 7-Day Treatment with the 5-HT2CAgonist Lorcaserin or the 5-HT2AAntagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.
abstract: Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT2Cagonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT2Ainverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT2Creceptor activation nor 5-HT2Areceptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT2Cagonists and 5-HT2Ainverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Matthew L
authors.identifier: http://orcid.org/0000-0003-4949-5246
authors.initials: ML
authors.lastname: Banks
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000008:administration & dosage*; D012055:Reinforcement Schedule; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D001552:Benzazepines; D010880:Piperidines; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C506658:lorcaserin; D014508:Urea; D003042:Cocaine; C510793:pimavanserin