Acute Amino Acid Loads That Deplete Brain Serotonin Fail to Alter Behavior

Abstract

Acute depletion of brain serotonin (5-HT) can be induced in both rats and humans by giving an amino acid load deficient in tryptophan (TRY). Because this treatment is relatively easy to administer and short-acting, it seems well suited for studying mood and/or behavioral changes linked to aberrant 5-HT functioning in humans. To investigate the ability of a TRY-deficient amino acid load to induce behavioral changes in animals, this study measured performance on an operant schedule of differential reinforcement of low rates of responding (DRL), locomotor activity in both novel and familiar environments, and paw-lick latencies on a hot-plate. All of these measures have been found previously to be altered by impairments of the brain 5-HT system. Adult male Sprague–Dawley rats were administered by gavage an amino acid load lacking TRY, an amino acid load containing TRY, or distilled water. Three hours later, behavioral tests were conducted. Although 5-HT levels were decreased in the hippocampus (−23.3%) and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in the striatum (−35.1%) and hippocampus (−38.5%), there were no effects of the TRY-deficient load on any of the behavioral tests. Because reliable mood-altering effects have been reported in human subjects using this method, their behavioral counterparts may be too subtle to observe in animals. Alternatively, effects observed in humans may reflect nonserotonergically mediated consequences of such tryptophan deficient amino acid loads and/or preexisting abnormalities of 5-HT or other systems in such people.