The discriminative stimulus effects of pentylenetetrazol
as a model of anxiety: recent developments

by
Jung ME, Lal H, Gatch MB.
Department of Pharmacology and Neuroscience,
University of North Texas Health Science Center,
3500 Camp Bowie Boulevard,
Fort Worth, TX 76107-2699, USA.
mjung@hsc.unt.edu
Neurosci Biobehav Rev. 2002 Jun;26(4):429-39


ABSTRACT

Pentylenetetrazol (PTZ), a GABA(A) receptor antagonist and prototypical anxiogenic drug, has been extensively utilized in animal models of anxiety. PTZ produces a reliable discriminative stimulus which is largely mediated by the GABA(A) receptor. Several classes of compounds can modulate the PTZ discriminative stimulus including 5-HT(1A), 5-HT(3), NMDA, glycine, and L-type calcium channel ligands. Spontaneous PTZ-lever responding is seen in trained rats during withdrawal from GABA(A) receptor compounds such as chlordiazepoxide and diazepam, and also ethanol, morphine, nicotine, cocaine, haloperidol, and phencyclidine. This effect is largely mediated by the GABA(A) receptor, which suggests that anxiety may be part of a generalized withdrawal syndrome mediated by the GABA(A) receptor. There are also important hormonal influences on PTZ. Corticosterone plays some role in mediation of its anxiogenic effects. There is a marked sex difference in response to the discriminative stimulus effects of PTZ, and estrogens appear to protect against its anxiogenic effects. Further work with the PTZ drug discrimination is warranted for characterization of anxiety during withdrawal, and the hormonal mechanisms of anxiety.
GABA(A)
Nicotine
Morphine
Diazepam
Lorazepam
Barbiturates
Meprobamate
Phencyclidine
Benzodiazepines
Future anxiolytics
Making animals cry
Anxiety and depression
Anxious golden hamsters
Better anti-anxiety drugs
Anxiolytics/antidepressants
Neurobiology and genetics of anxiety
Anxioselective compounds and GABA(A)
GABAergic dysfunction in mood disorders


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