Elevated startle during withdrawal from acute morphine: a model of opiate withdrawal and anxiety.
BACKGROUND
An elevated startle response has been observed in humans and animals during withdrawal from multiple substances of abuse, a phenomenon thought to reflect the anxiogenic effects of withdrawal. Although anxiety is a common symptom of opiate withdrawal, few studies have examined the effects of morphine withdrawal on acoustic startle.


OBJECTIVE
To develop a procedure for assessing opiate dependence through measurement of the startle reflex in rats.


METHODS
The effects of opiate withdrawal on startle were evaluated using both spontaneous and naloxone-precipitated withdrawal from an acute dose of morphine. The ability of the treatment drugs clonidine and chlordiazepoxide to block withdrawal-induced increases in startle was also tested.


RESULTS
Spontaneous withdrawal from an injection of morphine sulfate produced a significant increase in acoustic startle 2 h (3.2 mg/kg) or 4 h (10 mg/kg) after drug administration. Morphine withdrawal (10 mg/kg morphine sulfate) precipitated by the opiate antagonist naloxone (2.5 mg/kg) also produced a significant increase in startle magnitude. This elevation of startle was blocked by both clonidine (35 microg/kg) and chlordiazepoxide (10 mg/kg).


CONCLUSIONS
These data demonstrate that both spontaneous and precipitated withdrawal from an acutely administered opiate produce anxiety-like effects on acoustic startle. This paradigm may be useful in the study of anxiety and the early mechanisms of drug dependence.
D000161:Acoustic Stimulation; D000208:Acute Disease; D000818:Animals; D002707:Chlordiazepoxide / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002707:Chlordiazepoxide; D009020:Morphine; D003000:Clonidine