Anxiolytic-like effects of morphine and buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone.

Abstract:

RATIONALE:Morphine and buprenorphine have analgesic and anxiolytic-like properties. While their analgesic effects have been well characterized, their anxiolytic-like properties have not. OBJECTIVES:Effects of acute morphine and buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and naloxone pretreatment were assessed. Effects of chronic morphine and buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined. MATERIALS AND METHODS:Fear-conditioned rats were given subcutaneous drug treatment immediately before testing for FPS. Experiment 1, rats were administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or buprenorphine (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline or naloxone (0.5 mg/kg) and 5 min later given saline, morphine (2.5 mg/kg), or buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of saline, morphine (10 mg/kg), or buprenorphine (0.25 mg/kg) for 7 days. Immediately before testing, saline-treated rats were given saline, morphine (2.5 mg/kg), or buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine (2.5 mg/kg) or buprenorphine (0.03 mg/kg), and buprenorphine-treated rats were given buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross-tolerance in analgesia were assessed via the tail-flick test, as were naloxone-precipitated withdrawal. RESULTS:Morphine and buprenorphine had parallel dose-response curves in blocking FPS, with buprenorphine 40 times more potent than morphine. Naloxone reversed these effects. Morphine and buprenorphine showed tolerance and cross-tolerance in their anxiolytic-like and analgesic effects. Chronic buprenorphine produced less withdrawal than chronic morphine. CONCLUSIONS:Cross-tolerance between morphine and buprenorphine suggests a common receptor mediating their anxiolytic-like and analgesic effects.

journal_title

Psychopharmacology

authors

Glover EM,Davis M

doi

10.1007/s00213-008-1112-0

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

167-80

issue

2

eissn

0033-3158

issn

1432-2072

journal_volume

198

pub_type

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