Task-dependent effects of the antidepressant/antipanic drug phenelzine on memory

Phenelzine (PLZ) is a non-selective monoamine oxidase (MAO) inhibitor commonly used to treat depression and panic disorder. In addition to increasing levels of biogenic amines in the brain, PLZ elevates brain levels of the amino acid gamma-aminobutyric acid (GABA; Baker et al. 1991; present study). Given the extensive evidence implicating biogenic amines and GABA in mnemonic processes, PLZ may affect learning and memory. To investigate this possibility, male Sprague-Dawley rats were given PLZ sulfate (15 or 30 mg/kg, based on free base weight) 2 h prior to training in a continuous multiple trial inhibitory avoidance (CMIA) and spatial water maze task. Retention was assessed 48 h later. The results indicated that PLZ enhanced CMIA and impaired water maze retention performance. Compared to control rats, rats given PLZ took significantly longer to re-enter the shock compartment and swam longer distances before reaching the escape platform on the retention tests. These effects of PLZ did not appear to be the result of PLZ-induced changes in acquisition or retrieval processes, activity levels, or footshock sensitivity. Combined, these findings indicate that PLZ influences memory in a task-dependent manner. These differential effects of PLZ may be the result of contrasting influences of GABA and biogenic amines on memory.