Experimental Manipulations Blunt Modifications to Changes in Brain Monoamine Levels Associated with Time Alone and Completely Reverse Stress, but not by Pb+/-Stress Related Modifications to These Trajectories

CORY-SLECHTA, D.A.; VIRGOLINI, M.B.; ROSSI-GEORGE, A; WESTON, D.D.; THIRUCHELVAM, M

BEHAVIOURAL BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2009 vol. 201 p. 76 - 87

0166-4328

This study sought to further understand how environmental conditions influence the outcomes of early developmental insults. It compared changes in monoamine levels in frontal cortex, nucleus accumbens and striatum of male and female Long-Evans rat offspring subjected to maternal Pbexposure (0, 50 or 150 ppm in drinking water from 2 mos pre-breeding until pup weaning) +/- prenatal (PS) (restraint on GD16-17) or PS + offspring stress (OS; 3 variable stress challenges to young adults) determined at 2 mos of age and at 6 mos of age in littermates subsequently exposed either to experimental manipulations (EM: daily handling and performance on an operant fixed interval (FI) schedule of food reward), or to no experience (NEM; time alone). Time alone (NEM conditions), even in normal (control) animals, modified the trajectory of neurochemical changes between 2 and 6 mos across brain regions and monoamines. EM significantly modified the NEM trajectories, and except NE and striatal DA, which increased, blunted the changes in monoamine levels that occurred over time alone. Pb+/stress modified the trajectory of monoamine changes in both EM and NEM conditions, but these predominated under NEM conditions. Stress-associated modifications, occurring mainly with NEMOS groups, were fully reversed by EM procedures, while reversals of Pb+/-stress-associated modifications occurred primarily in nucleus accumbens, a region critical to mediation of FI response rates. These results extend the known environmental conditions that modify developmental Pb+/-stress insults, which is critical to ultimately understanding whether early insults lead to adaptive ormaladaptive behavior and to devising behavioral therapeutic strategies. That time alone and a set of EMconditions typically used as outcome measures in intervention studies can themselves invokeneurochemical changes, moreover, has significant implications for experimental design of such studies.Keywords: behavior, lead, prenatal stress, offspring stress, dopamine, serotonin, norepinephrine,enrichment