The effect of serotonin depletion on rat adaptive behavior in high and low responders to novelty

Adaptive behavioral responses to repeated daily testing in the open field test (OFT) were studied in rats that had a different locomotor response to a novel environment (ambulatory scores above and below the median, respectively). A clear‐cut progressive habituation of exploratory activity was observed over the 5 daily sessions, but was more pronounced in HR (high responders) than in LR (low responders). p‐Chlorophenylalanine‐induced serotonin depletion, confirmed biochemically by high‐performance liquid chromatography (HPLC), attenuated the rate of behavioral habituation in the LR and HR (to a minor degree), and abolished the between group differences in motor activity in the OFT. Autoradiography revealed a significantly greater specific binding of the GABAA receptor agonist, [3H]muscimol, to the entorhinal cortex of LR than to the entorhinal cortex of HR rats, and a near‐significant trend within the dentate gyrus of the hippocampus, but not within other brain structures. In conclusion, serotonin was found to contribute in a complex way to the habituation of locomotor activity, an effect that depended on the initial level of locomotor activity. The intrinsic mechanism underlying the observed effects might involve changes in central GABAA receptors.