Time-dependent changes in brain monoamine oxidase activity and in brain levels of monoamines and amino acids following acute administration of the antidepressant/antipanic drug phenelzine

Phenelzine (PLZ) is a non-selective monoamine oxidase (MAO) inhibitor commo nly used to treat depression and panic disorder. Acute administration of PL Z produces several neurochemical changes, including an increase in brain le vels of the catecholamines norepinephrine (NE) and dopamine (DA), of 5-hydr oxytryptamine (5-HT), and of the amino acids alanine and gamma-aminobutyric acid (GABA). The goal of the present series of experiments was to characte rize the time course of these PLZ-induced changes. Male Sprague-Dawley rats were sacrificed 6, 24, 48, 96, 168, or 336 hr after acute PLZ administrati on (15 or 30 mg/kg, i.p., based on free base weight). Whole brain levels of monoamines and amino acids were determined using HPLC, and MAO A and B act ivities were determined using a radiochemical procedure. The results indica ted that PLZ changed amino acid levels 6 and 24 hr after injection, but not 48 hr later. In contrast, the effects of PLZ on MAO activity and monoamine s were longer-lasting. For example, PLZ-induced increases in dopamine and 5 -HT were observed 1 week after injection, and PLZ-induced inhibition of MAO activity persisted for 2 weeks. Thus, in addition to demonstrating that th e effects of PLZ on MAO activity and monoamines were long-lasting, these re sults indicate that the effects of PLZ on MAO activity and on brain levels of monoamines and amino acids are temporally dissociated. These findings re garding the long-term effects of PLZ on neurochemistry will have considerab le critical implications for the design and interpretation of behavioral st udies of the acute effects of PLZ. (C) 2000 Elsevier Science Inc.