The behavioral pharmacology of zolpidem

Evidence for the functional significance of α1-containing GABAA receptors

Amanda C. Fitzgerald, Brittany T. Wright, Scott Heldt

Research output: Contribution to journalReview article

16 Citations (Scopus)

Abstract

Rationale: Zolpidem is a positive allosteric modulator of γ-aminobutyric acid (GABA) with preferential binding affinity and efficacy for α1-subunit containing GABAA receptors (α1-GABA ARs). Over the last three decades, a variety of animal models and experimental procedures have been used in an attempt to relate the behavioral profile of zolpidem and classic benzodiazepines (BZs) to their interaction with α1-GABAARs. Objectives: This paper reviews the results of rodent and non-human primate studies that have evaluated the effects of zolpidem on motor behaviors, anxiety, memory, food and fluid intake, and electroencephalogram (EEG) sleep patterns. Also included are studies that examined zolpidem's discriminative, reinforcing, and anticonvulsant effects as well as behavioral signs of tolerance and withdrawal. Results: The literature reviewed indicates that α1-GABAARs play a principle role in mediating the hypothermic, ataxic-like, locomotor- and memory-impairing effects of zolpidem and BZs. Evidence also suggests that α1-GABAARs play partial roles in the hypnotic, EEG sleep, anticonvulsant effects, and anxiolytic-like of zolpidem and diazepam. These studies also indicate that α1-GABAARs play a more prominent role in mediating the discriminative stimulus, reinforcing, hyperphagic, and withdrawal effects of zolpidem and BZs in primates than in rodents. Conclusions: The psychopharmacological data from both rodents and non-human primates suggest that zolpidem has a unique pharmacological profile when compared with classic BZs. The literature reviewed here provides an important framework for studying the role of different GABAAR subtypes in the behavioral effects of BZ-type drugs and helps guide the development of new pharmaceutical agents for disorders currently treated with BZ-type drugs.

Original languageEnglish (US)
Pages (from-to)1865-1896
Number of pages32
JournalPsychopharmacology
Volume231
Issue number9
DOIs
StatePublished - Jan 1 2014

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GABA-A Receptors
Benzodiazepines
Pharmacology
Primates
Rodentia
Anticonvulsants
Electroencephalography
Sleep
Pharmaceutical Preparations
Aminobutyrates
zolpidem
Anti-Anxiety Agents
Diazepam
Hypnotics and Sedatives
gamma-Aminobutyric Acid
Anxiety
Animal Models
Eating

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

The behavioral pharmacology of zolpidem : Evidence for the functional significance of α1-containing GABAA receptors. / Fitzgerald, Amanda C.; Wright, Brittany T.; Heldt, Scott.

In: Psychopharmacology, Vol. 231, No. 9, 01.01.2014, p. 1865-1896.

Research output: Contribution to journalReview article

Fitzgerald, Amanda C. ; Wright, Brittany T. ; Heldt, Scott. / The behavioral pharmacology of zolpidem : Evidence for the functional significance of α1-containing GABAA receptors. In: Psychopharmacology. 2014 ; Vol. 231, No. 9. pp. 1865-1896.
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