Neurochemical and behavioral consequences of mild, uncontrollable shock: Effects of PCPA

The present experiments examined the role of the serotonergic system in the behavioral deficit produced by uncontrollable shock. In Experiment 1: Establishment of model, the behavioral potential of the Sprague-Dawley rat was defined. When exposed to mild uncontrollable stress such as a 0.8 mA electric footshock, a significant percentage of rats developed a shock escape deficit which was evident when subsequently placed in a shock escape paradigm. Serotonin depletion was produced by chronic treatment with p-chlorophenylalanine. Biogenic amine levels and 5-HT levels were monitored in various brain areas using HPLC. Following chronic treatment with PCPA, the shock escape capability of the Sprague-Dawley rat was assessed. The severe depletion of 5-HT in various brain regions was highly correlated with a dramatic improvement in the shock escape scores. Thus, the detrimental effects of exposure to a mild course of inescapable shock can be prevented by chronic treatment with PCPA. These experiments implicate the serotonergic system as a possible mediator of the "learned helplessness" phenomenon.