Bidirectional cross-tolerance between methadone (mu) - and ethylketocyclazocine (kappa) - tolerant rats

Oksoon Hong, Gerald A. Young, Naim Khazan

Research output: Contribution to journalArticle

Abstract

Our laboratory previously reported on unidirectional cross-tolerance between morphine and methadone, both mu opioid agonists, and between morphine and ethylketocyclazocine (EKC), the latter being a relatively selective kappa opioid agonist. Morphine-tolerant rats were found to be non-cross-tolerant to methadone and EKC, but methadone- and EKC-tolerant rats were cross tolerant to morphine. In the present study, we characterized the cross-tolerance between methadone and EKC. A group of female adult Sprague-Dawley rats was made tolerant to methadone by a series of automatic i.v. injections ranging from 0.25 mg/kg per 2 h on the first day to 2.0 mg/kg per 1.5 h on the ninth day. Another group of rats was similarly made tolerant to EKC with doses ranging from 0.5 mg/kg per 2 h on the first day to 4 mg/kg per h on the ninth day. Relatively similar degrees of tolerance development to the EEG and behavioral effects of methadone and EKC were reflected by decreases in durations of action and decreases in opioid-induced EEG power spectral changes. Methadone-tolerant rats were found to be cross-tolerant to the EEG and behavioral effects of EKC, and, similarly, EKC-tolerant rats were found to be crosstolerant to those of methadone. Thus, a bidirectional cross-tolerance between a mu and a kappa agonist was demonstrated. The present results together with those reported earlier indicate that cross-tolerance may not be directly related to the receptor selectivity of the opioids. It is possible that differential physicochemical properties of these opioids may play a more decisive role in the phenomenon of cross-tolerance.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalDrug and Alcohol Dependence
Volume18
Issue number1
DOIs
StatePublished - 1986
Externally publishedYes

Fingerprint

Ethylketocyclazocine
Methadone
tolerance
Rats
Morphine
Opioid Analgesics
Electroencephalography
Opioid Receptors
Sprague Dawley Rats

Keywords

  • Cross-tolerance
  • EEG
  • Ethylketocyclazocine
  • Methadone
  • Opioids

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

Bidirectional cross-tolerance between methadone (mu) - and ethylketocyclazocine (kappa) - tolerant rats. / Hong, Oksoon; Young, Gerald A.; Khazan, Naim.

In: Drug and Alcohol Dependence, Vol. 18, No. 1, 1986, p. 87-96.

Research output: Contribution to journalArticle

Hong, Oksoon ; Young, Gerald A. ; Khazan, Naim. / Bidirectional cross-tolerance between methadone (mu) - and ethylketocyclazocine (kappa) - tolerant rats. In: Drug and Alcohol Dependence. 1986 ; Vol. 18, No. 1. pp. 87-96.
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