Neonatal lesions of the ventral tegmental area affect monoaminergic responses to stress in the medial prefrontal cortex and other dopamine projection areas in adulthood.

A mean decrease of dopamine (DA) to 20% and serotonin to 25-30% of control levels was found in the medial prefrontal cortex (mPFC) and amygdala/piriform cortex (A/PC) of adult rats with neonatal lesions of the ventral tegmental area (VTA). The metabolites were less decreased suggesting an increased activity of the remaining terminals. Moderate decreases to 30-75% were detected for DA and serotonin in the nucleus accumbens, olfactory tubercle and striatum. Footshock stress in control animals resulted in a strong increase (200% of control) in DA metabolites in mPFC and A/PC. The noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in A/PC was strongly increased to 240%. When stress was given to the neonatally VTA-lesioned animals these neurochemical responses were reduced compared to the nonlesioned rats. In the case of DA in the mPFC this was clearly due to a loss of stress response in the severe lesion group where DA is depleted to less than 20% of control. The stress-induced small increases in DA metabolism in tubercle, accumbens and striatum and serotonin metabolism in the striatum (20-40%) were entirely lost, while the MHPG increase in the A/PC was blunted. The present results suggest that moderate and severe lesions of DA and serotonin alter or prevent the normal activation of these transmitter systems and even of the noradrenergic system to stress.