Kb. Kumar et al., PHENYTOIN AND PHENOBARBITAL - A COMPARISON OF THEIR STATE-DEPENDENT EFFECTS, Pharmacology, biochemistry and behavior, 47(4), 1994, pp. 951-956
Two commonly used antiepileptic drugs, phenytoin sodium and phenobarbi
tal sodium, were investigated for state-dependency effects at differen
t doses. Male Wistar strain rats trained to a criterion in an inhibito
ry avoidance task and a food-motivated T-maze task under varying drug
and nondrug states were subjected to retention tests 24 and 48 h, resp
ectively, following acquisition. The treatment instituted at the time
of retrieval was either the same as, or different from, that used duri
ng training. The results indicated that phenytoin produced state-depen
dency effects at test doses of 20, 40, and 60 mg/kg in the avoidance t
ask and at test dose of 20 mg/kg in the T-maze task experiments. These
state-specific effects were comparable to those of phenobarbital sodi
um (5 and 10 mg/kg). The reinstitution of the drug state in an additio
nal test session produced approximately equal and significant recovery
of conditioned responses in the T-maze paradigm both in phenytoin and
phenobarbital groups. These results demonstrate, for the first time,
the ability of phenytoin to produce state-dependency effects in a patt
ern similar to that observed with a widely studied compound such as ph
enobarbital. Overall, the data provide no support for the view that th
e degree of discriminability of a drug is an indicator of potential st
ate-dependency effects and is restricted only to the dosage high enoug
h to produce noticeable intoxication.