Rastogi S K, Wenger G R, McMillan D E
Arch Int Pharmacodyn Ther. 1985 Aug;276(2):247-62.
The effects of the d and l optical isomers of methadone and (S)-(-)- and (R)-(+)- optical isomers of pentobarbital were studied on responding maintained under a multiple fixed-ratio 30-response fixed-interval 5-min schedule of food presentation in rats before, during, and after chronic administration of d- or l- methadone. Acute administration of both isomers of pentobarbital decreased responding more during the fixed-ratio component of the schedule than during the fixed-interval component. S-(-)-pentobarbital was slightly more potent than R-(+)-pentobarbital in decreasing the rate of fixed-ratio responding and the fixed-interval quarter life. Daily administration of d-methadone for four weeks shifted the dose-effect curves for (S)-(-)-pentobarbital to the right for both schedule components; however, (R)-(+)-pentobarbital showed less tendency to shift. Daily administration of l-methadone showed little tendency to shift the dose-effect curve for either pentobarbital isomer. Before chronic treatment, acute administration of l-methadone, decreased rates of both FR and FI responding at much lower doses than d-methadone. Unlike d-methadone, chronic daily l-methadone shifted the l-methadone dose-effect curves to the right during both components of the schedule.