Predictable stress promotes place preference and low mesoaccumbens dopamine response

Aversive stimuli that are signaled, and therefore predictable, are preferred to unsignaled ones and promote less severe stress-related disturbances. Since stressful events are known to activate mesoaccumbens dopamine (DA) transmission, in the present experiments, we evaluated possible differences in mesoaccumbens DA response to predictable and unpredictable footshocks. Mice of the inbred strain DBA/2 were trained for conditioned place preference (CPP) in shuttle boxes. The procedure promoted significant preference for the compartment previously paired with predictable shocks (PR) to that paired with unpredictable shocks (NP). Mesoaccumbens levels of DA and its metabolites were therefore evaluated either after the first or the last (third) training session. A significant increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were observed in animals exposed for the first time to the apparatus without shock delivery (SHAM) or to the PR and NP conditions compared with unhandled mice. There was no difference between PR and NP values, and DOPAC and HVA levels in both groups differed from those observable in the SHAM-exposed group. However, trained mice exposed to NP showed a significant elevation of DOPAC and HVA levels in comparison with those exposed to PR. These results show that information about predictability of aversive stimuli reduces central stress responses and suggest a possible relationship between reduced stressfulness and preference for predictable aversive experiences.