Modulation of morphine-induced EEG and behavioral effects by dynorphin A-(1-13) in non-tolerant and morphine-tolerant rats

The purpose of the present study was to assess effects of dynorphin A-(1-13) on morphine-induced changes in electroencephalographic (EEG) spectral power and morphine-induced suppression of slow-wave sleep in non-tolerant and morphine-tolerant rats. Adult female Sprague-Dawley rats were implanted with chronic cortical EEG electrodes, electromyographic electrodes in the temporalis muscle and with intracerebroventricular (i.c.v.) cannulae and, in some cases, additional intravenous (i.v.) cannulae. Injections of morphine (i.c.v., 20 μg/rat) produced a biphasic EEG and behavioral response, composed of 2–3 hr of slow-wave bursts and increased spectral power (0–4 Hz) in the EEG, associated with behavioral stupor, followed by 2–3 hr of EEG and behavioral arousal. Dynorphin (i.c.v., 20 μg/rat), administered 10 min before injections of morphine in non-tolerant rats, antagonized morphine-induced increases in spectral power of the EEG and morphine-induced suppression of slow-wave sleep. In addition, EEG power spectra obtained after intraventricular administration of morphine from rats, treated with dynorphin and morphine intraventricularly 24 hr earlier, were qualitatively similar to those previously found after acute administration of kappa opioid agonists. In morphine-tolerant rats, pretreatment with dynorphin given intraventricularly, 10 min prior to intraventricular administration of morphine, restored morphine-induced increases in EEG spectral power and suppression of slow-wave sleep. The results suggest that dynorphin may modulate the characteristics of opioid receptors.