title: Orexin-1 receptor antagonism does not reduce the rewarding potency of cocaine in Swiss-Webster mice.
abstract: The orexin family of hypothalamic neuropeptides has been implicated in reinforcement mechanisms relevant to both food and drug reward. Previous behavioral studies with antagonists at the orexin A-selective receptor, OX(1), have demonstrated its involvement in behavioral sensitization, conditioned place-preference, and self-administration of drugs of abuse. Adult male Swiss-Webster mice were implanted with stimulating electrodes to the lateral hypothalamus and trained to perform intracranial self-stimulation (ICSS). The effects of the OX(1)-selective antagonist SB 334867 on brain stimulation-reward (BSR) and cocaine potentiation of BSR were measured. SB 334867 (10-30mg/kg, i.p.) alone had no effect on ICSS performance or BSR threshold. Cocaine (1.0-30mg/kgi.p.) dose-dependently potentiated BSR, measured as lowering of BSR threshold. This effect was not blocked by 30mg/kg SB 334867 at any cocaine dose tested. In agreement with previous reports, SB 334867 resulted in a reduction of body weight 24h after acute administration. Based on these data, it is concluded that orexins acting at OX(1) do not contribute to BSR; and are not involved in the reward-potentiating actions of cocaine on BSR. The data are discussed in the context of prior findings of SB 334867 effects on drug-seeking and drug-consuming behaviors.
authors: Laboratory of Developmental Neuropharmacology, Department of Neurology, University of North Carolina at Chapel Hill, USA.
authors: Thorfinn T
authors: TT
authors: Riday
authors: Eric W
authors: EW
authors: Fish
authors: J Elliott
authors: JE
authors: Robinson
authors: Thomas M
authors: TM
authors: Jarrett
authors: Megan M
authors: MM
authors: McGuigan
authors: C J
authors: CJ
authors: Malanga
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009287:Naphthyridines; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D018765:Dopamine Uptake Inhibitors; D009287:Naphthyridines; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014508:Urea; D003042:Cocaine