title: Effects of the δ opioid agonist AZD2327 upon operant behaviors and assessment of its potential for abuse.
abstract: AZD2327 is a brain-penetrant agonist at δ opioid receptors which has antidepressant and anxiolytic properties in a wide array of animal models. As part of the preclinical safety pharmacology assessment, a number of studies were conducted in order to characterize its behavioral effects and its potential for abuse, in order to enable testing in humans. AZD2327 produced only modest effects when tested in a multiple fixed-ratio differential reinforcement of low rate schedule in rats, and did not enhance the rate-suppressing effects of ethanol in the procedure. In a suppressed responding test, AZD2327 only reduced rates of unpunished responding. In drug discrimination studies, AZD2327 produced partial or no generalization from known drugs of abuse. In primates trained to self-administer cocaine, substitution with AZD2327 did not result in appreciable self-administration of AZD2327, indicating that it does not behave as a positive reinforcer under the present conditions. Following termination of repeated administration of AZD2327, no signs of physical dependence (withdrawal) were noted. Overall, the data suggest that AZD2327 does not possess a high potential for abuse, and appears to have only subtle behavioral effects as measured by operant behaviors.
authors.affiliation: Departments of Neuroscience, AstraZeneca R & D Wilmington, United States. Electronic address: Thomas.Hudzik@Abbvie.com.
authors.forename: T J
authors.initials: TJ
authors.lastname: Hudzik
authors.affiliation: Safety Assessment, AstraZeneca R & D Wilmington, United States.
authors.forename: M R
authors.initials: MR
authors.lastname: Pietras
authors.affiliation: Safety Assessment, AstraZeneca R & D Wilmington, United States.
authors.forename: R
authors.initials: R
authors.lastname: Caccese
authors.affiliation: DMPK, AstraZeneca R & D Wilmington, United States.
authors.forename: K H
authors.initials: KH
authors.lastname: Bui
authors.affiliation: Departments of Neuroscience, AstraZeneca R & D Wilmington, United States.
authors.forename: F
authors.initials: F
authors.lastname: Yocca
authors.affiliation: McLean Hospital, Harvard University Medical School, Cambridge, MA, United States.
authors.forename: C A
authors.initials: CA
authors.lastname: Paronis
authors.affiliation: AstraZeneca R & D Sodertalje, Sweden.
authors.forename: M D B
authors.initials: MD
authors.lastname: Swedberg
mesh_terms: D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012453:Saimiri; D012646:Self Administration
chemical_list: C560622:4-((3-aminophenyl)(4-(4-fluorobenzyl)piperazin-1-yl)methyl)-N,N-diethylbenzamide; D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta
keywords: AZD2327; Abuse potential; Operant behavior