Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABAA/α1 receptors

  title={Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABAA/$\alpha$1 receptors},
  author={James K. Rowlett and Roger D. Spealman and Snjezana Lelas and James M. Cook and Wenyuan Yin},
Abstract Rationale. The discriminative stimulus effects of zolpidem in squirrel monkeys trained at doses greater than or equal to 3.0 mg/kg differ from those of conventional benzodiazepines (BZs), but the extent to which these effects reflect the selectivity of zolpidem for GABAA/α1 receptors is not known. Objectives. The present study investigated the ability of GABAA/α1-preferring agonists to substitute for training doses of zolpidem greater than or equal to 3.0 mg/kg and the ability of GABAA… 

Zolpidem generalization and antagonism in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.

Ethanol and zolpidem share similar discriminative stimulus effects most likely through GABA(A) receptors that contain alpha(1) subunits, however, antagonism by Ro15-4513 of zolPidem generalization from the lower training dose of ethanol (1.0 g/kg) may involve additional zol pidem-sensitive GABA(B) receptor subtypes (e.g., alpha(2/3) and alpha(5)).

Contribution of α1GABAA and α5GABAA Receptor Subtypes to the Discriminative Stimulus Effects of Ethanol in Squirrel Monkeys

Ethanol's ability to enhance GABA neurotransmission via GABAA receptors has been implicated as an important mechanism underlying its discriminative stimulus (DS) effects in animals and subjective

Negative GABAA modulators attenuate the discriminative stimulus effects of benzodiazepines and the neuroactive steroid pregnanolone in rhesus monkeys

Negative modulators are qualitatively similar to neutral modulators in diazepam-treated animals; however, interactions between negative modulators and midazolam suggest that different receptors mediate the effects of some (DMCM) and not other (β-CCM)negative modulators.

The behavioral pharmacology of zolpidem: evidence for the functional significance of α1-containing GABAA receptors

The psychopharmacological data from both rodents and non-human primates suggest that zolpidem has a unique pharmacological profile when compared with classic BZs.

Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABAA receptor subtypes

The results suggest that the α1GABAA receptor subtype plays a key role in benzodiazepine-induced increases in consumption of palatable food, whereas the α5GAB AA receptor sub type may not be involved in this effect.

Benzodiazepines and heightened aggressive behavior in rats: reduction by GABAA/α1 receptor antagonists

The carboline derivatives, β-CCt and 3-PBC, antagonists with preferential action at the GABAA receptors with α1 subunits, may antagonize benzodiazepine-heightened aggression, thus implicating the α1Subunit in heightened aggression.

Little evidence of a role for the α1GABAA subunit-containing receptor in a rhesus monkey model of alcohol drinking.

Alcohol-drinking animals appeared more sensitive to the effects of GABAergic compounds on drinking behavior, and results do not support a strong contribution of α1GABAA receptors to the reinforcing effects of alcohol in primates.

GABAA/α1 receptor agonists and antagonists: effects on species-typical and heightened aggressive behavior after alcohol self-administration in mice

Benzodiazepine antagonists, particularly those acting preferentially at GABAA/α1 subunit-containing receptors, decrease alcohol-heightened and species-typical aggressive behavior, but are ineffective in attenuating the sedative effects of alcohol.

Selective Antagonism of GABAA Receptor Subtypes: An In Vivo Approach to Exploring the Therapeutic and Side Effects of Benzodiazepine–Type Drugs

Results indicate that subtype-selective antagonists represent a useful approach to studying receptor mechanisms underlying the behavioral effects of BZ-type drugs.



Discriminative stimulus effects of zolpidem in squirrel monkeys: comparison with conventional benzodiazepines and sedative-hypnotics.

The view that zolpidem's selectivity for the alpha1-subunit of the BZ/gamma-aminobutyric acid(A) receptor complex confers a distinctive profile of interoceptive effects that overlaps partially with those of typical BZs but not withThose of barbiturates is supported.

Transduction of the discriminative stimulus effects of zolpidem by GABAA/α1 receptors

Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs

BZ agonists can be distinguished on the basis of substitution for triazolam and, thus, the triazlam discrimination may be a useful tool for identifying compounds of different efficacy at BZ receptors.

Transduction of the discriminative stimulus effects of zolpidem by GABA(A)/alpha1 receptors.

Findings offer the first evidence for a selective role of GABA(A)/alpha1 receptors in the interoceptive effects of high doses of zolpidem in squirrel monkeys trained to discriminate a high dose from saline.

The discriminative stimulus properties of zolpidem, a novel imidazopyridine hypnotic

Differences between the discriminative stimulus produced by zolpidem in rats and those produced by other sedatives may be due to a selective action of zolPidem on a sub-type of benzodiazepine binding site.

Behavioral Pharmacology of Zolpidem Relative to Benzodiazepines A Review

  • C. Rush
  • Psychology, Biology
    Pharmacology Biochemistry and Behavior
  • 1998

The discriminative stimulus effects of diazepam in rats at two training doses.

Two groups of rats were trained to discriminate either a low (1 mg/kg) or a high intraperitoneal dose of diazepam from vehicle injections in a two-lever, food-reinforcement procedure, and stimulus generalization to benzodiazepine agonists and partial agonists was tested.

Drug discrimination analysis of midazolam under a three-lever procedure. II: Differential effects of benzodiazepine receptor agonists.

  • C. SannerudN. Ator
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1995
This three-choice drug discrimination procedure appears to be a useful model for studying relative intrinsic efficacies of this class of compounds and the differential effects of the classic 1,4 benzodiazepine agonists tested suggest that the discriminative stimulus effects of these other compounds may be more differentiable than previous drug discrimination studies have suggested.

Mechanism of action of the hypnotic zolpidem in vivo

It is established that the sedative‐hypnotic and anticonvulsant activities of zolpidem are due to its action on α1‐GABAA receptors and not on α2‐ or α3‐GabAA receptors.

High-Dose Discrimination Training with Midazolam Context Determines Generalization Profile

  • N. Ator
  • Biology, Medicine
    Pharmacology Biochemistry and Behavior
  • 1999