Changes in urination/defecation, auditory startle response, and startle-induced ultrasonic vocalizations in rats undergoing morphine withdrawal: similarities and differences between acute and chronic dependence.
In drug-free subjects, a single dose of morphine followed by an opioid antagonist a few hours later results in signs of a withdrawal syndrome, suggesting a state of physical dependence. Increased urination/defecation, altered startle, and ultrasonic vocalizations (USV) are some signs of the withdrawal syndrome in rats chronically dependent on morphine. We investigated whether naltrexone stimulates urination/defecation and alters startle and USV in male rats that were pretreated with only a single dose of morphine and compared these indices to the ones of chronic dependence. Separate groups of rats were pretreated with either a single dose (10 mg/kg) or with a continuous s.c. infusion of morphine via an osmotic pump. Naltrexone (0.01-1.0 mg/kg) was administered 2 to 6 h after the single dose of morphine and on days 7 to 11 of the infusion. Immediately after the naltrexone injection subjects were placed in sound-attenuating boxes to record startle and USV and to collect urine/feces. Subjects chronically exposed to morphine also were tested during spontaneous withdrawal 3 to 24 h after pump removal. Naltrexone increased urination/defecation in subjects pretreated with morphine either chronically or acutely; it increased startle and USV in acutely dependent rats but decreased them in chronically dependent rats. In the latter group, changes in the four variables during spontaneous withdrawal were qualitatively similar to those during precipitated withdrawal but smaller in magnitude. Differences in withdrawal signs between acute and chronic dependence suggest that the neural substrates that mediate those particular components of the withdrawal syndrome are affected differently in the two states of dependence.
Kalinichev
Mikhail
M
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Holtzman
Stephen G
SG
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D003672:Defecation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology* / Q000523:psychology; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology; D014465:Ultrasonics; D014554:Urination / Q000187:drug effects / Q000502:physiology*; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology*
D009271:Naltrexone