REPEATED ADMINISTRATIONS OF (-)-DEPRENYL INCREASE [H-3] MK801 BINDINGIN RAT-BRAIN AND ANTAGONIZE THE IMPAIRMENT OF PASSIVE-AVOIDANCE CONDITIONING INDUCED BY N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS

Repeated but not single administrations of the MAO type B inhibitor (- )-deprenyl (1 mu mol/kg s.c. for 21 consecutive days) antagonized the impairment of passive avoidance retention induced by the N-methyl-D-as partate (NMDA) receptor antagonists 2-amino-5-phosphonovalerate (APV), ketamine and dizocilpine (MK801), in rats. In well-washed membranes p repared from the hippocampi of rats repeatedly treated with (-)-depren yl, the [H-3]MK801 specific binding was increased. In contrast, repeat ed MAO B-selective doses of pargyline or (+)-amphetamine, as well as s ingle injections with (-)-deprenyl failed to change [H-3]MK801 binding . It is suggested that the effects of repealed (-)-deprenyl administra tions upon NMDA receptors and upon the impairment of acquisition of a passive avoidance task induced by NMDA antagonists could be independen t of MAO inhibition.