Lorcaserin decreases the reinforcing effects of 3,4‐methylenedioxypyrovalerone (MDPV) and cocaine in Sprague‐Dawley rats

Abstract

Lorcaserin is a serotonin (5‐HT) 2C receptor‐preferring agonist that is currently approved by the Food and Drug Administration to treat obesity; however, its behavioral effects are also mediated by 5‐HT 2A and 1A receptors. Agonists acting at 5‐HT2C receptors are known to dampen dopamine neurotransmission, an effect that could be beneficial for treating drug abuse. 3,4‐Methylenedioxypyrovalerone (MDPV) is a cocaine‐like monoamine reuptake inhibitor that is commonly found in abused bath salt preparations. Recent studies have demonstrated lorcaserin decreases the reinforcing effects of cocaine in rats and monkeys, and the present study aimed to: (1) determine whether lorcaserin was equally effective at decreasing the reinforcing effects of MDPV and cocaine; and (2) determine the receptor(s) responsible for the effects of lorcaserin on cocaine and MDPV self‐administration. Male Sprague‐Dawley rats (n=6) were injected with lorcaserin (0.1–5.6 mg/kg, IP) 25 minutes before the initiation of MDPV or cocaine self‐administration sessions. Lorcaserin was equipotent at suppressing responding for MDPV and cocaine; however, individual differences in sensitivity to lorcaserin were observed. To determine which receptor mediated the effects of lorcaserin, rats were administered 5‐HT1A (WAY100635, 0.178 mg/kg), 5‐HT2A (MDL100907, 0.1 mg/kg), or 5‐HT2C (SB242084, 0.1 mg/kg) receptor antagonists (IP) 15 minutes prior to lorcaserin treatment. Antagonism of 5‐HT2C (but not 5‐HT1A or 5‐HT2A) receptors reversed the effects of lorcaserin on MDPV and cocaine self‐administration. Taken together, these data indicate lorcaserin may be an effective pharmacotherapy against MDPV and cocaine abuse through its agonist actions at 5‐HT2C receptors.Support or Funding InformationThis research was supported by the National Institutes of Health (NIH) and the National Institute on Drug Abuse (NIDA) R01DA039146 (GTC) and T32DA031115 and the NIH Intramural Research Programs of the NIDA and the National Institute of Alcohol Abuse and Alcoholism (NIAAA) (KCR).