Muscimol-like discriminative stimulus effects of GABA agonists in rats

Hendrée E. Jones, Robert L. Balster

Research output: Contribution to journalArticle

Abstract

The discriminative stimulus effects of GABAergic drugs were evaluated in rats trained to discriminate the direct GABA(A) agonist, muscimol (1.0 mg/kg IP), from saline under a two-lever fixed ratio (FR) 32 schedule of food reinforcement. Another direct GABA, agonist, THIP, produced full substitution for muscimol, however, at doses producing response rate decreasing effects. Diazepam, an allosteric modulator of GABA-mediated postsynaptic inhibition, yielded a maximum of 50% muscimol-lever responding at a dose that also decreased rates of responding. Partial substitution for muscimol (maximal levels of 71% muscimol-lever responding) was also produced by the GABA agonist progabide. Propofol, an anesthetic that potentiates GABA(A) receptor function, and the GABA uptake inhibitor, tiagabine, produced no greater than 53 and 48% muscimol-lever responding, respectively. Valproic acid, a reversible GABA transaminase inhibitor, failed to substitute for muscimol, and vigabatrin, an irreversible GABA transaminase inhibitor, yielded a maximal 46% muscimol-lever responding. These results demonstrate the pharmacological specificity of muscimol discrimination by showing that only direct agonists for the GABA site on the GABA, receptor complex produce full substitution. GABA agonists acting by other mechanisms can be distinguished from muscimol and THIP in this procedure.

Original languageEnglish (US)
Pages (from-to)319-326
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume59
Issue number2
DOIs
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

GABA Agonists
Muscimol
Rats
4-Aminobutyrate Transaminase
Substitution reactions
GABA Modulators
GABA Uptake Inhibitors
Vigabatrin
GABA-A Receptor Agonists
Reinforcement Schedule
GABA Receptors
Valproic Acid
Propofol
GABA-A Receptors
Diazepam
Anesthetics
Reinforcement
Pharmacology

Keywords

  • Diazepam
  • Drug discrimination
  • GABA (gamma-aminobutyric acid)
  • GABA transaminase inhibitors
  • Muscimol
  • Rats
  • THIP
  • Valproic acid
  • Vigabatrin

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Muscimol-like discriminative stimulus effects of GABA agonists in rats. / Jones, Hendrée E.; Balster, Robert L.

In: Pharmacology Biochemistry and Behavior, Vol. 59, No. 2, 02.1998, p. 319-326.

Research output: Contribution to journalArticle

Jones, Hendrée E. ; Balster, Robert L. / Muscimol-like discriminative stimulus effects of GABA agonists in rats. In: Pharmacology Biochemistry and Behavior. 1998 ; Vol. 59, No. 2. pp. 319-326.
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