Acute morphine induces oscillatory discharge of noradrenergic locus coeruleus neurons in the waking monkey.
Neurons were recorded extracellularly from the locus coeruleus (LC) of a waking, chair-restrained cynomolgus monkey before and for 0.5-4 h after intramuscular injections of morphine sulfate (0.3-10 mg/kg). Tonic discharge of each LC neuron tested (n = 11) decreased after morphine injection; this effect appeared to be dose-dependent for the range of 0.3-3.0 mg/kg. Unexpectedly, these same doses of morphine also induced a pronounced burst-pause discharge pattern in all LC neurons recorded. Thus, whereas in the naive animal pauses in discharge longer than 3 s were rare during waking, after morphine injection LC neurons frequently exhibited pauses in impulse activity of 10 s or longer during non-drowsy waking. The bursts in activity following morphine corresponded to orienting behaviors or apparent alertness, whereas pauses were associated with eye closure or slowly drifting gaze. Closer analysis revealed that this burst-pause activity pattern was somewhat regular, with a period of about 15-35 s. This observation was confirmed by autocorrelogram analysis. In view of previous findings in rodent LC, we suggest that acute morphine elicits a dual effect on primate LC neurons: inhibition of discharge by direct effects on opiate receptors located on LC cells, and periodic phasic activation mediated by excitatory afferents to the LC.
Aston-Jones
G
G
Department of Mental Health Sciences, Hahnemann University Medical School, Philadelphia, PA 19102.
Rajkowski
J
J
Kubiak
P
P
Akaoka
H
H
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects*
D009020:Morphine; D009638:Norepinephrine