OPPOSITE RESPONSES OF MESOLIMBIC DOPAMINE SYSTEM TO CONTROLLABLE AND UNCONTROLLABLE AVERSIVE EXPERIENCES

It has been previously shown that rodents exposed to stressful experiences show a biphasic response of the mesolimbic dopamine (DA) system, that is, initial increase of DA release followed by a decrease below control levels (Puglisi-Allegra et al., 1991). Evidence is now presented showing that mice exposed to a series of foot shocks show an increase of DA release in the nucleus accumbens septi (NAS) if they are allowed to control the shock experience (shocked condition) and a decrease of DA release in this brain area if they are not allowed to exert any control (yoked condition). These results indicate that escapable/controllable and inescapable/uncontrollable aversive experiences elicit opposite responses from the mesolimbic DA system. Mice exposed to the apparatus without receiving shock (sham condition) show a time-dependent biphasic evolution mesolimbic DA release in line with previous reports indicating that confinement in an unknown environment represents a stressful experience for mice. Moreover, exposure to the sham condition for a time comparable to the duration of shock and yoked exposure induces a mesolimbic DA response only quantitatively different from the response of the yoked group but qualitatively different from the response of the shocked mice. These results suggest that in environmental conditions that allow behavioral control, enhanced mesolimbic DA release is maintained regardless of the intensity of the aversive stimuli. On the other hand, evaluation of changes in acid DA metabolites levels in the frontal cortex (FC) of mice exposed to the shocked, yoked, and sham conditions suggests that stressful experiences characterized by a different intensity of the aversive stimuli could elicit graded responses in the FC DA system. Taken together, the present results may indicate that the initial activation of the mesolimbic DA system induced by stressful experiences accompanies the organism's attempts to cope behaviorally with such a pressure while the subsequent inhibition takes over when, despite the efforts made by the organism, no behavioral coping is possible.