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Effects of acute morphine withdrawal on ultrasonic vocalizations in adult rats: unchanged 50-kHz call rate and altered subtype profile

Abstract

Rationale

Adult rat 22- and 50-kHz ultrasonic vocalizations (USVs) are commonly considered as indices of negative and positive affect, respectively. More specifically, we have proposed that positive affective states are revealed by a predominance of trill over flat 50-kHz call subtypes. However, the 50-kHz call subtypes emitted during aversive drug states remain largely uninvestigated.

Objectives

To determine whether acute morphine withdrawal affects 50-kHz call rates or alters the relative prevalence of trill and flat calls.

Methods

In experiment 1, adult male rats were given saline or morphine (6 mg/kg SC), then acutely challenged 4 h later with saline or naloxone (1 mg/kg SC), and recorded 10–30 min post-injection. In experiments 2 and 3, rats received saline or morphine (6 mg/kg), followed 4 h later by acute saline or naloxone (0.1 mg/kg) challenge; USVs were subsequently recorded during 30-min place conditioning sessions.

Results

Naloxone (0.1 mg/kg) produced a strong conditioned place aversion only after acute morphine pretreatment, consistent with antagonist-precipitated morphine withdrawal. The morphine-naloxone combination decreased the relative prevalence of trills and promoted flat calls. Naloxone given alone (0.1 and 1 mg/kg) inhibited trill calls but did not significantly alter the prevalence of flat calls, whereas morphine given alone (4 h pre-session) was largely without effect. Fifty-kHz call rates were inhibited by naloxone given alone, but otherwise unaffected. Twenty-two-kHz calls were sparse.

Conclusions

The 50-kHz call subtype shift seen during antagonist-precipitated morphine withdrawal was opposite in direction to that previously associated with rewards, and hence may reveal negative affect.

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Acknowledgements

Supported by a Natural Science and Engineering Research Council of Canada (NSERC) discovery grant (155055, to P.B.S.C) and NSERC Undergraduate Student Research Awards (to YQ.C.L. and L.Z.). P.B.S.C. is a member of the Center for Studies in Behavioral Neurobiology at Concordia University, Montreal. We wish to thank Jodie Huang for helping with data collection. The authors have no financial relationship with the organizations that sponsored this research. All experiments comply with the current laws of Canada.

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Correspondence to Paul B. S. Clarke.

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All procedures were approved by the McGill Animal Care Committee in accordance with the guidelines of the Canadian Council on Animal Care.

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Lin, Y.C., Zhao, L.L. & Clarke, P.B.S. Effects of acute morphine withdrawal on ultrasonic vocalizations in adult rats: unchanged 50-kHz call rate and altered subtype profile. Psychopharmacology 235, 1945–1953 (2018). https://doi.org/10.1007/s00213-018-4891-y

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  • DOI: https://doi.org/10.1007/s00213-018-4891-y

Keywords

  • Morphine
  • Withdrawal
  • Naloxone
  • Opioid
  • Ultrasonic vocalization
  • Aversion