Effects of buprenorphine, a new narcotic agonist-antagonist analgesic on the EEG, power spectrum and behavior of the rat

The acute effects of buprenorphine, a new narcotic agonist-antagonist. on the central nervous system have been investigated in unanesthetized. freely-moving rats utilizing EEG and behavioral parameters. The rats were prepared with chronic cortical and temporalis muscle electrodes for continuous recording of EEG and EMG and gross behavior for 3 days before and 3–4 days after acute intravenous administration of physiological saline, morphine or buprenorphine at several doses. Generally, narcotic agonists, like morphine, produce a biphasic pattern of initial behavioral stupor with high-voltage EEG slow-bursting activity, followed by behavioral arousal with low-voltage desynchronous EEG. Sleep and REM sleep appear at about 3 hr after a 10 mg/kg dose of morphine. In the present study, buprenorphine, being a partial agonist of the morphine type produced a similar biphasic effect at low doses. But on quantitation of duration of stupor and arousal, an inverted U-shaped function resulted. Increasing doses up to 1 mg/kg increased the duration of stupor to a maximum and further increase to 10 or 30 mg/kg decreased the duration of stupor. Also, increasing doses up to 10 mg/kg increased the duration of arousal to a maximum. However, further increase to 30 mg/kg actually decreased the duration of arousal. Computer-derived EEG spectral power between 0–10 Hz also showed an inverted U-shaped relation to doses from 0.3 to 10 mg/kg. with a maximal power at 1 mg/kg associated with maximal EEG synchrony. These findings demonstrate a dose-dependent agonist-antagonist action of buprenorphine. At low to intermediate doses, it has narcotic agonist action. But at higher doses, it manifests antagonistic action by blocking its own agonist effects.