Elsevier

Neuropharmacology

Volume 19, Issue 9, September 1980, Pages 845-850
Neuropharmacology

Eeg and behavioral effects of ethylketocyclazocine, morphine and cyclazocine in rats: Differential sensitivities towards naloxone

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Abstract

The effects of ethylketocyclazocine were compared with those of morphine and cyclazocine on the cortical EEG and spontaneous behavior of unrestrained, male Sprague-Dawley rats. Intraperitoneal administration of ethylketocyclazocine (2.5 mg/kg), morphine (10 mg/kg), and cyclazocine (2.5 mg/kg) each induced alterations in the EEG and behavior of rats characterized by high-voltage synchrony associated with behavioral stupor during wakefulness. Both ethylketocyclazocine and morphine produced biphasic EEG and behavioral profiles consisting of an initial phase of EEG synchrony and stupor followed by a period of EEG activation and behavioral arousal. In contrast, the profile of cyclazocine was not biphasic but was distinguished by intermittent periods of behavioral excitation and EEG desynchronization. When the rats were pretreated with naloxone (0.01–10 mg/kg, s.c. at −10 min), there was a dose-related antagonism of the duration of EEG synchrony and stupor produced by the three analgesics. Ethylketocyclazocine was the most sensitive to naloxone (AD 50 dose of naloxone = 0.035 mg/kg) and cyclazocine was the least sensitive (AD 50 = 2.1 mg/kg). Antagonism of the drug-induced increase in latency to slow-wave sleep was dose-related for ethylketocyclazocine and morphine, but not for cyclazocine. The ability to identify differences between these three analgesics, based on their respective EEG and behavioral profiles and their sensitivities to naloxone, is consistent with current theories of multiple opiate receptors mediating certain pharmacological effects of opioids.

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    A preliminary report of this research was presented at the International Narcotics Research Conference, North Falmouth, Massachusetts, June 11–15, 1979.

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