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

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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 5min 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.

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Acknowledgements

The authors would like to thank Stephen Holtzman for his generosity in providing the tail-flick apparatus used in this study. This research was supported by NIMH Grants MH47840 and MH072850 to MD, the Woodruff Foundation, the National Science Foundation Science and Technology Center (the Center for Behavioral Neuroscience of the National Science Foundation under Agreement No. IBN-9876754) and, in part by RROO165 to the Yerkes National Primate Center and an American Psychological Association Mental Health Fellowship granted to Ebony Glover. Portions of this work were presented at the 36th annual meeting of the Society for Neuroscience and submitted by Ebony M. Glover to the Department of Psychology, Emory University, in partial fulfillment of the requirements for the doctoral degree. Animals used in this study were cared for in accordance with guidelines of the Emory University Institutional Animal Care and Use Committee.

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  1. Department of Psychology, Emory University, Atlanta, GA, USA

    Ebony M. Glover & Michael Davis

  2. Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience and the Yerkes National Primate Research Center, Emory University, Yerkes Neuroscience Building, Rm. 5214, 954 Gatewood Rd NE, Atlanta, GA, USA

    Ebony M. Glover

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  1. Ebony M. Glover
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Correspondence to Ebony M. Glover.

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Glover, E.M., Davis, M. Anxiolytic-like effects of morphine and buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone. Psychopharmacology 198, 167–180 (2008). https://doi.org/10.1007/s00213-008-1112-0

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