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 μg/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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Acknowledgements The authors wish to thank David Atkinson, Stephanie Hanes, and Michelle Pilat and for their assistance in conducting the experiments. In addition, we thank Drs. Lisa Schrott, Monica Luciana, and Megan Gunnar of the University of Minnesota for helpful discussion of the manuscript. This work was supported by the National Institute on Drug Abuse T32 DA07097 and the University of Minnesota.
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