Anxiolytic effect of serotonin depletion in the novelty-induced hypophagia test

Rationale Relatively little is known about the neural mechanisms underlying anxiety in the novelty-induced hypophagia test, the only known anxiety test that is responsive to chronic but not acute or subchronic antidepressant treatment. Objectives The goal of the present experiment was to characterize the role of serotonin in the ability of novelty to suppress feeding. Materials and methods Pair-housed male Sprague-Dawley rats were trained to eat graham cracker crumbs individually in their home cage (15 min/day). After stable daily intakes were obtained, the animals were depleted of serotonin using 4-chloro-DL-phenylalanine (150 mg kg(-1) day(-1)x2 days). Forty-eight hours later, central serotonin was restored by the administration of the peripheral L-aromatic amino acid decarboxylase inhibitor, benserazide (10 mg/kg), followed 15 min later with the immediate precursor of serotonin, 5-hydroxy-L-tryptophan (30 mg/kg). Thirty minutes later, the animals were given access to graham cracker crumbs in a novel environment. Results The animals demonstrated increased latencies to approach the food and reduced food intake in the novel environment. This effect was attenuated by serotonin depletion. Repletion of central serotonin restored the inhibitory response to novelty. The analysis of serotonin content in different brain regions confirmed that serotonin was depleted by greater than 90%, whereas the repletion treatment resulted in serotonin levels similar to nondepleted animals. Conclusions Acute depletion of serotonin acts to reduce anxiety behavior as measured by an inhibitory anxiety response during exposure to novel stimuli. These findings are in agreement with the proposed general role for serotonin in behavioral inhibition and that reductions of serotonin facilitate the adoption of more active coping responses to stress.