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
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
.