Zolpidem, triazolam, and diazepam decrease distress vocalizations in mouse pups: differential antagonism by flumazenil and beta-Carboline-3-carboxylate-t-butyl ester (beta-CCt).

Abstract

In response to stressful events, neonatal mice emit ultrasonic vocalizations (USVs), which are suppressed by BZ agonists. The present study examined the role of the benzodiazepine/alpha1 (BZ/alpha1) receptor subtype in the suppression engendered by the BZ/alpha1-preferring agonist zolpidem and the nonselective BZ agonists triazolam and diazepam. The role of BZ receptor subtypes was explored further by conducting antagonism studies using the BZ/alpha1-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt), in comparison with the nonselective BZ antagonist flumazenil. Mouse pups (CFW strain) were separated from their dam and littermates at day 7, and placed for 4 min in a test chamber with reduced ambient temperature (19 +/- 1 degrees C) for recording USVs, motor incoordination (measured as a pup rolling on its back per grid cross), and body temperature. Zolpidem, triazolam, and diazepam suppressed USVs in a dose-dependent manner, concomitant with increases in incoordination and augmentation of hypothermia. These effects of the three BZ agonists were blocked by flumazenil in a manner consistent with surmountable antagonism. The ability of zolpidem, but not triazolam or diazepam, to suppress USVs and augment hypothermia was antagonized by beta-CCt, whereas the increase in motor incoordination engendered by zolpidem, triazolam, and diazepam was not sensitive to beta-CCt administration. Collectively, these results suggest that zolpidem suppresses distress USVs in mouse pups by a mechanism distinct from that of typical BZs. Furthermore, suppression of distress USVs by zolpidem may involve BZ/alpha1 receptors and a nonanxiolytic mechanism, such as hypothermia.

• Authors: J K Rowlett, W Tornatzky, J M Cook, C Ma, K A Miczek
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 297 Issue 1 Pg. 247-53 (Apr 2001) ISSN: 0022-3565 [Print] United States
• PMID: 11259551 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Anxiety Agents
• Carbolines
• GABA-A Receptor Antagonists
• Pyridines
• Receptors, GABA-A
• Triazolam
• Flumazenil
• Zolpidem
• tert-butyl beta-carboline-3-carboxylate
• Diazepam

Topics

• Animals
• Animals, Newborn
• Anti-Anxiety Agents (pharmacology)
• Body Temperature (drug effects)
• Carbolines (pharmacology)
• Diazepam (pharmacology)
• Dose-Response Relationship, Drug
• Flumazenil (pharmacology)
• GABA-A Receptor Antagonists
• Mice
• Pyridines (pharmacology)
• Receptors, GABA-A (physiology)
• Triazolam (pharmacology)
• Vocalization, Animal (drug effects)
• Zolpidem