Andrew C Harris1, Jonathan C Gewirtz. 1. Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA.
Abstract
RATIONALE: 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.
RATIONALE: 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.
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