Continuous quantitative monitoring of spontaneous opiate withdrawal: locomotor activity and sleep disorders.
The time course of drug abstinence is not readily amenable to examination using intermittent observations, because abstinence is known to interfere with circadian rhythms of general activity. Accordingly, we propose a model for continuous assessment of spontaneous withdrawal without any intervention by the investigator. This model is based on the automatic recording of locomotor activity. Experiments were performed in rectangular activity cages equipped with two infrared photoelectric cells. In a parallel experiment, to confirm the locomotor activity effects, continuous monitoring of EEG activities was achieved from two cortical and one reference electrodes. Morphine dependence was induced by intraperitoneal injections of increasing doses of morphine twice daily for 10 days (from 5 up to 90 mg/kg). Behavioral and EEG activities were recorded for 8 to 10 days following the last injection of morphine. Although control rats displayed a typical locomotor activity pattern characterized by nocturnal hyperactivity that was markedly reduced during the light phase, opiate abstinent rats developed a constant motor activity during the first 3 or 4 postinjection days and that was associated with a drastic reduction of overall rapid eye movement sleep (REM) and non-REM sleep and with an increase of waking (W). Although morphine-abstinent rats slowly resumed a normal circadian cycle after the fourth day in terms of horizontal activity, REMS, NREMS and W, long-term effects were revealed by the permanent motor instability recorded during both the light and the dark phases when the total amount of photocell counts was considered, and by the perturbation of the circadian rhythm of the ratio of REM sleep to total sleep time. Automatic continuous recording of total motor behavior appears to be a useful index with which to follow, over an extended period of time, the acute and long-term consequences of opiate abstinence. Therefore, long-term withdrawal-induced changes in activity could be a suitable model for the validation of antiabstinence therapies.
Stinus
L
L
Laboratoire de Neuropsychobiologie de Désadaptations, Université de Bordeaux II, INSERM U-259, France.
Robert
C
C
Karasinski
P
P
Limoge
A
A
D000701:Analgesics, Opioid / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D016903:Drug Monitoring / Q000379:methods*; D004569:Electroencephalography / Q000187:drug effects; D009020:Morphine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012893:Sleep Wake Disorders / Q000139:chemically induced*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D000701:Analgesics, Opioid; D009020:Morphine