Activation of GLP-1 receptors attenuates oxycodone taking and seeking without compromising the antinociceptive effects of oxycodone in rats

摘要

Systemic administration of exendin-4 attenuates oxycodone self-administration in rats and does not alter the thermal antinociceptive effects of oxycodone. Rats were pretreated with systemic infusions of vehicle or exendin-4 prior to oxycodone self-administration test sessions maintained on FR5 or PR schedules. Food intake, water consumption, and body weight were measured up to 24 h post infusion and thermal nociception was measured before exendin-4 pretreatment and after oxycodone self-administration test sessions (a). In FR5 test sessions, total active lever responses (b) and total oxycodone infusions (c) were significantly decreased in rats (n = 20/treatment) pretreated with 0.3 and 3.0 µg/kg exendin-4 versus vehicle (*p < 0.05, Bonferroni). In PR test sessions, total active lever responses (d) in rats (n = 8/treatment) pretreated with 0.3 and 3.0 µg/kg exendin-4 were significantly decreased compared with vehicle (*p < 0.05, Bonferroni). Total oxycodone infusions (e) in rats pretreated with 0.3 µg/kg exendin-4, and breakpoints (f) in rats pretreated with 3.0 µg/kg exendin-4 were decreased compared with vehicle (*p < 0.05, Bonferroni). Tail-flick latencies were significantly increased after oxycodone self-administration test sessions compared to baseline measurements (g), indicating a thermal analgesic response (*p < 0.05; n = 9/treatment). Percentage maximum possible effect (%MPE) was not significantly different between rats pretreated with exendin-4 and those pretreated with vehicle, indicating no effect of exendin-4 on oxycodone-induced analgesic responses in this model (h)