Abstract
To understand the role of serotonin (5-hydroxytryptamine; 5-HT) -1A receptors in the treatment of anxiety and the development of tolerance to benzodiazepines the present study was designed to monitor the responsiveness of postsynaptic 5-HT-1A receptors following repeated administration of diazepam and buspirone. Results show that tolerance in the anxiolytic profile is produced following repeated administration (2 weeks) of diazepam (2 mg/kg) but not buspirone (0.5 mg/kg). The behavioral effects of 8-OH-DPAT at a dose of 0.25 mg/kg were monitored 3 days after repeated administration of saline or buspirone or diazepam. The results show that 8-OH-DPAT elicited forepaw treading was smaller in repeated diazepam but not repeated buspirone injected rats, while hyperlocomotive effects of 8-OH-DPAT were smaller in both repeated buspirone and repeated diazepam injected rats. The results suggest that postsynaptic 5-HT-1A receptor-dependent responses were attenuated following long-term administration of diazepam but not buspirone. Role of 5-HT-1A receptors in the development of tolerance to the anxiolytic effects of diazepam but not buspirone is discussed.
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The authors would like to thank Karachi University for research grant.
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Khan, A., Haleem, D.J. Tolerance in the Anxiolytic Profile Following Repeated Administration of Diazepam but not Buspirone is Associated with a Decrease in the Responsiveness of Postsynaptic 5-HT-1A Receptors. BIOLOGIA FUTURA 58, 345–357 (2007). https://doi.org/10.1556/ABiol.58.2007.4.2
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DOI: https://doi.org/10.1556/ABiol.58.2007.4.2