Studies on cyproheptadine-amphetamine interaction after pretreatment with 6-hydroxydopamine

6-hydroxydopamine (6-OH-DA) and cyproheptadine (CPH) exerted a lowering effect on blood amphetamine (AMPH) level in rats, at the same time the content of AMPH in the brain was elevated and the simultaneously recorded stereotypy was higher than in controls. After joint premedication with 6-OH-DA and CPH, however, no cumulative effect on AMPH brain level was seen, the highest AMPH elevation in whole brain as well as in corpus striatum occurred in animals premedicated with 6-OH-DA only. In spite of that, the highest stereotypy scores were noted after joint premedication with both substances. This may indicate that CPH premedication causes a rise in AMPH stereotypy mainly by pharmacodynamic interaction, though the elevation of the content of AMPH in the brain after CPH and 6-OH-DA must be of some influence as well. A further result is worth noting. After destroying peripheral adrenergic structures by 6-OH-DA a change from a two-compartment to a one-compartment model of AMPH kinetics occurred. This indicates that these structures may play the role of the second compartment or a part of it.