TY - JOUR
T1 - The discriminative stimulus effects of pentylenetetrazol as a model of anxiety
T2 - Recent developments
AU - Jung, Marianna E.
AU - Lal, Harbans
AU - Gatch, Michael B.
PY - 2002/6
Y1 - 2002/6
N2 - Pentylenetetrazol (PTZ), a GABAA 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 GABAA receptor. Several classes of compounds can modulate the PTZ discriminative stimulus including 5-HT1A, 5-HT3, NMDA, glycine, and L-type calcium channel ligands. Spontaneous PTZ-lever responding is seen in trained rats during withdrawal from GABAA receptor compounds such as chlordiazepoxide and diazepam, and also ethanol, morphine, nicotine, cocaine, haloperidol, and phencyclidine. This effect is largely mediated by the GABAA receptor, which suggests that anxiety may be part of a generalized withdrawal syndrome mediated by the GABAA 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.
AB - Pentylenetetrazol (PTZ), a GABAA 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 GABAA receptor. Several classes of compounds can modulate the PTZ discriminative stimulus including 5-HT1A, 5-HT3, NMDA, glycine, and L-type calcium channel ligands. Spontaneous PTZ-lever responding is seen in trained rats during withdrawal from GABAA receptor compounds such as chlordiazepoxide and diazepam, and also ethanol, morphine, nicotine, cocaine, haloperidol, and phencyclidine. This effect is largely mediated by the GABAA receptor, which suggests that anxiety may be part of a generalized withdrawal syndrome mediated by the GABAA 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.
KW - Corticosterone
KW - Estrogen
KW - Ethanol withdrawal
KW - GABA antagonist
KW - Pentylenetetrazol
UR - http://www.scopus.com/inward/record.url?scp=0036627615&partnerID=8YFLogxK
U2 - 10.1016/S0149-7634(02)00010-6
DO - 10.1016/S0149-7634(02)00010-6
M3 - Review article
C2 - 12204190
AN - SCOPUS:0036627615
SN - 0149-7634
VL - 26
SP - 429
EP - 439
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
IS - 4
ER -