Effects of the δ opioid agonist AZD2327 upon operant behaviors and assessment of its potential for abuse

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 potent...

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Bibliographic Details
Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2014-09, Vol.124, p.48-57
Main Authors: Hudzik, T.J., Pietras, M.R., Caccese, R., Bui, K.H., Yocca, F., Paronis, C.A., M.D.B., Swedberg
Format: Article
Language:English
Subjects:
Abuse potential
Animals
AZD2327
Benzamides - administration & dosage
Benzamides - pharmacokinetics
Benzamides - pharmacology
Conditioning, Operant - drug effects
Female
Humans
Macaca mulatta
Male
Operant behavior
Piperazines - administration & dosage
Piperazines - pharmacokinetics
Piperazines - pharmacology
Rats
Rats, Long-Evans
Receptors, Opioid, delta - agonists
Saimiri
Self Administration
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Summary: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. •AZD2327, a selective δ-opioid agonist, has modest effects upon operant behavior in the rat.•The modest effects distinguish delta opioid agonists from other opioids, such as μ and κ agonists.•AZD2327 lacked anxiolytic-like effects in the squirrel monkey, unlike rat.•AZD2327 is not self-administered by rhesus monkeys, suggesting its abuse liability is low.•AZD2327 produces discriminative stimulus effects which are distinct from abused drugs.•AZD2327 produces convulsions in monkeys, unlike rats.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2014.05.009