DISCRIMINATIVE STIMULUS EFFECTS OF PRESYNAPTIC GABA AGONISTS IN PENTOBARBITAL-TRAINED RATS

Citation
Dm. Grech et Rl. Balster, DISCRIMINATIVE STIMULUS EFFECTS OF PRESYNAPTIC GABA AGONISTS IN PENTOBARBITAL-TRAINED RATS, Pharmacology, biochemistry and behavior, 47(1), 1994, pp. 5-11
Citations number
50
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00913057
Volume
47
Issue
1
Year of publication
1994
Pages
5 - 11
Database
ISI
SICI code
0091-3057(1994)47:1<5:DSEOPG>2.0.ZU;2-P
Abstract
The discriminative stimulus effects of indirect-acting GABAergic drugs were compared to those of pentobarbital (PB) and midazolam in rats tr ained to discriminate 5 mg/kg PB from saline under a two-lever fixed-r atio 32 schedule of food reinforcement. PB and midazolam produced dose -dependent substitution for the training dose of PB with response rate reduction only at doses above those producing full substitution. Valp roic acid, an antiepileptic drug and GABA transaminase inhibitor, subs tituted for PB but only at a dose that produced response rate suppress ion. Vigabatrin, an irreversible GABA transaminase inhibitor, failed t o substitute for PB, but did produce a dose-dependent decrease in resp onse rates. The GABA uptake inhibitors, -[bis[4-(trifluoromethyl)pheny l]-methoxy]ethyl]-1, 2,5,6-tetrahydro-3-pyridinecarboxylic acid (CI-96 6) and (R(-)-N-[4,4-bis(3-methylthien-2-yl)but-3-enyl] nipecotic acid HCl (tiagabine), produced no greater than 40% PB-lever responding. Ami nooxyacetic acid (AOAA), which is described as a nonselective presynap tic GABA agonist, yielded a maximum of 43% PR-lever responding. These results indicate that the discriminative stimulus effects of the indir ect GABA(A) agonists, PB and midazolam, although similar to one anothe r, differ from those of presynaptic GABAergic drugs. Differences in th e discriminative stimulus properties of GABA transaminase inhibitors a nd uptake inhibitors also exist, indicating that not all presynaptic G ABA agonists have similar behavioral profiles. These results contribut e to a further understanding of the similarities and differences in th e behavioral effects of drugs that enhance GABAergic neurotransmission .