TY - JOUR
T1 - Inhibition of cocaine and 3,4-methylenedioxypyrovalerone (MDPV) self-administration by Lorcaserin is mediated by 5-HT2C receptors in rats
AU - Gannon, Brenda M.
AU - Sulima, Agnieszka
AU - Rice, Kenner C.
AU - Collins, Gregory T.
N1 - Funding Information:
This research was supported by grants from the National Institute on Drug Abuse [R01DA039146 and T32DA031115] at the National Institutes of Health. The work of the Drug Design and Synthesis Section was supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health. https://doi.org/10.1124/jpet.117.246082.
PY - 2018/2
Y1 - 2018/2
N2 - Lorcaserin is a serotonin (5-HT) 2C receptor-preferring agonist approved by the US Food and Drug Administration to treat obesity. Lorcaserin decreases cocaine self-administration in rats and monkeys. Although this effectis partially inhibited bya 5-HT 2C receptor antagonist (SB242084), lorcaserin also has effects at 5-HT 2A and 5-HT 1A receptors, and the relative contribution of these receptors to its anti-cocaine effects has not been investigated. The goals of this study were to determine 1) the potency and effectiveness of lorcaserin to decrease self-administration of cocaine and 3,4-methylenedioxypyrovalerone (MDPV), a common "bath salts" constituent; and 2) the receptor(s) mediating the effects of lorcaserin on cocaine and MDPV self-administration. Male Sprague-Dawley rats (n = 6) were trained to self-administer MDPV under a progressive ratio schedule of reinforcement and maintained under this schedule with daily access to 0.32 mg/kg per infusion of cocaine or 0.032 mg/kg per infusion of MDPV. Dose-response curves for the effects of lorcaserin on cocaine and MDPV self-administration were generated by administering lorcaserin (0.1-5.6 mg/kg) 25 minutes before the start of the session. To assess the effects of 5-HT 2C (SB242084, 0.1 mg/kg), 5-HT 2A (MDL100907, 0.1 mg/kg), and 5-HT 1A (WAY100635, 0.178 mg/kg) receptor antagonists, they were administered 15 minutes before lorcaserin. Lorcaserin decreased cocaine and MDPV self-administration with equal potency. Antagonism of 5-HT 2C (but not 5-HT 1A or 5-HT 2A ) receptors blocked the effects of lorcaserin on cocaine and MDPV self-administration. Taken together, these data provide additional support for further development of 5-HT 2C receptor agonists, such as lorcaserin, for the treatment of stimulant abuse.
AB - Lorcaserin is a serotonin (5-HT) 2C receptor-preferring agonist approved by the US Food and Drug Administration to treat obesity. Lorcaserin decreases cocaine self-administration in rats and monkeys. Although this effectis partially inhibited bya 5-HT 2C receptor antagonist (SB242084), lorcaserin also has effects at 5-HT 2A and 5-HT 1A receptors, and the relative contribution of these receptors to its anti-cocaine effects has not been investigated. The goals of this study were to determine 1) the potency and effectiveness of lorcaserin to decrease self-administration of cocaine and 3,4-methylenedioxypyrovalerone (MDPV), a common "bath salts" constituent; and 2) the receptor(s) mediating the effects of lorcaserin on cocaine and MDPV self-administration. Male Sprague-Dawley rats (n = 6) were trained to self-administer MDPV under a progressive ratio schedule of reinforcement and maintained under this schedule with daily access to 0.32 mg/kg per infusion of cocaine or 0.032 mg/kg per infusion of MDPV. Dose-response curves for the effects of lorcaserin on cocaine and MDPV self-administration were generated by administering lorcaserin (0.1-5.6 mg/kg) 25 minutes before the start of the session. To assess the effects of 5-HT 2C (SB242084, 0.1 mg/kg), 5-HT 2A (MDL100907, 0.1 mg/kg), and 5-HT 1A (WAY100635, 0.178 mg/kg) receptor antagonists, they were administered 15 minutes before lorcaserin. Lorcaserin decreased cocaine and MDPV self-administration with equal potency. Antagonism of 5-HT 2C (but not 5-HT 1A or 5-HT 2A ) receptors blocked the effects of lorcaserin on cocaine and MDPV self-administration. Taken together, these data provide additional support for further development of 5-HT 2C receptor agonists, such as lorcaserin, for the treatment of stimulant abuse.
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U2 - 10.1124/jpet.117.246082
DO - 10.1124/jpet.117.246082
M3 - Article
C2 - 29217539
AN - SCOPUS:85041227927
SN - 0022-3565
VL - 364
SP - 359
EP - 366
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -