The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments.
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.
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
Marianna E
ME
Jung
Harbans
H
Lal
Michael B
MB
Gatch
D000818:Animals; D001008:Anxiety Disorders / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents / Q000494:pharmacology; D023421:Models, Animal; D009538:Nicotine / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D018009:Receptors, Glycine / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012737:Sex Factors; D013331:Strychnine / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
D020746:Calcium Channels, L-Type; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018684:Glycine Agents; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D012701:Serotonin; D009538:Nicotine; D013331:Strychnine; D010433:Pentylenetetrazole