Thermal sensitivity as a measure of spontaneous morphine withdrawal in mice

Rebecca E. Balter, Linda A. Dykstra

Research output: Research - peer-reviewArticle

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Abstract

Introduction: Opioid withdrawal syndrome is a critical component of opioid abuse and consists of a wide array of symptoms including increases in pain sensitivity (hyperalgesia). A reliable preclinical model of hyperalgesia during opioid withdrawal is needed to evaluate possible interventions to alleviate withdrawal. The following study describes a method for assessing increases in thermal sensitivity on the hotplate in a mouse model of spontaneous morphine withdrawal. Methods: C57BL/6J mice received 5.5. days of 30, 56, or 100. mg/kg morphine or saline (s.c., twice daily). In Experiment I, thermal sensitivity data were collected at baseline and at 8, 24, 32, 48. h and 1. week following the final injection. Thermal sensitivity was assessed by examining latency to respond on a hotplate across a range of temperatures (50, 52, 54, and 56 °C). In Experiment II, 0.01. mg/kg buprenorphine was administered 30. min prior to each testing session during the withdrawal period. In Experiment III, jumping during a 30. min period was assessed at baseline and at 0, 8, 24, 32, and 48. h following the final morphine injection. Results: During the withdrawal period, thermal sensitivity increased significantly in all morphine-treated mice as compared to saline-treated mice. Thermal sensitivity was greater in mice treated with 56. mg/kg morphine compared to 30. mg/kg and peaked earlier than in mice treated with 100. mg/kg (32. h v 1. wk). The increase in thermal sensitivity following 56. mg/kg morphine was attenuated by a dose of buprenorphine that did not produce antinociception alone (i.e., 0.01. mg/kg). In general, the results of the jumping experiment paralleled those obtained in Experiment I. Discussion: Response latency on the hotplate is a reliable and sensitive measure of spontaneous morphine withdrawal in mice, making it an ideal behavior for assessing the potential of medications and environmental interventions to alleviate opioid withdrawal.

LanguageEnglish (US)
Pages162-168
Number of pages7
JournalJournal of Pharmacological and Toxicological Methods
Volume67
Issue number3
DOIs
StatePublished - May 2013

Fingerprint

Morphine
Hot Temperature
Experiments
Opioid Analgesics
Buprenorphine
Hyperalgesia
Injections
Inbred C57BL Mouse
Reaction Time
Pain
Temperature
Testing

Keywords

  • Jumping
  • Methods
  • Morphine
  • Mouse
  • Spontaneous withdrawal
  • Thermal sensitivity

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Thermal sensitivity as a measure of spontaneous morphine withdrawal in mice. / Balter, Rebecca E.; Dykstra, Linda A.

In: Journal of Pharmacological and Toxicological Methods, Vol. 67, No. 3, 05.2013, p. 162-168.

Research output: Research - peer-reviewArticle

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abstract = "Introduction: Opioid withdrawal syndrome is a critical component of opioid abuse and consists of a wide array of symptoms including increases in pain sensitivity (hyperalgesia). A reliable preclinical model of hyperalgesia during opioid withdrawal is needed to evaluate possible interventions to alleviate withdrawal. The following study describes a method for assessing increases in thermal sensitivity on the hotplate in a mouse model of spontaneous morphine withdrawal. Methods: C57BL/6J mice received 5.5. days of 30, 56, or 100. mg/kg morphine or saline (s.c., twice daily). In Experiment I, thermal sensitivity data were collected at baseline and at 8, 24, 32, 48. h and 1. week following the final injection. Thermal sensitivity was assessed by examining latency to respond on a hotplate across a range of temperatures (50, 52, 54, and 56 °C). In Experiment II, 0.01. mg/kg buprenorphine was administered 30. min prior to each testing session during the withdrawal period. In Experiment III, jumping during a 30. min period was assessed at baseline and at 0, 8, 24, 32, and 48. h following the final morphine injection. Results: During the withdrawal period, thermal sensitivity increased significantly in all morphine-treated mice as compared to saline-treated mice. Thermal sensitivity was greater in mice treated with 56. mg/kg morphine compared to 30. mg/kg and peaked earlier than in mice treated with 100. mg/kg (32. h v 1. wk). The increase in thermal sensitivity following 56. mg/kg morphine was attenuated by a dose of buprenorphine that did not produce antinociception alone (i.e., 0.01. mg/kg). In general, the results of the jumping experiment paralleled those obtained in Experiment I. Discussion: Response latency on the hotplate is a reliable and sensitive measure of spontaneous morphine withdrawal in mice, making it an ideal behavior for assessing the potential of medications and environmental interventions to alleviate opioid withdrawal.",
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