Sleep disruption and increased apneas after pontine microinjection of morphine

The medial pontine reticular formation (mPRF) is a cholinoceptive brain stem region known to play a key role in regulating rapid eye movement (REM) sleep and state-dependent ventilatory depression. Numerous lines of evidence have shown that opioids inhibit both cholinergic neurotransmission and REM sleep. The present study examined the hypothesis that morphine applied to the cholinoceptive mPRF would inhibit REM sleep and alter ventilation. In six cats, guide cannulas were chronically implanted to permit pontine microinjection of morphine sulfate, naloxone, and the cholinergic agonist carbachol. After each mPRF microinjection, 2-h polygraphic recordings quantified respiratory frequency and the percent of time spent in states of wakefulness, non-REM sleep, and REM sleep. The results show that mPRF administration of morphine significantly inhibited REM sleep and that this REM sleep inhibitory effect was blocked by pretreating the mPRF with naloxone. Apneic episodes were increased after injection of morphine alone, and the apneas were decreased by the cholinergic agonist carbachol. The results also demonstrated that the ability of microinjected morphine to inhibit REM sleep was dose-dependent and site-dependent. Considered together, the site-localization, pharmacologic blocking, and dose-response data support the hypothesis that specific regions of the mPRF can contribute to the long-recognized ability of morphine to inhibit REM sleep and alter respiratory control.