The effects of selective stimulation of perikarya, but not axons of passage, within the ventral tegmental area (VTA) on the locus coeruleus (LC) noradrenergic system were examined. Anterograde and combined retrograde-immunohistochemical studies indicated both dopaminergic and non-dopaminergic projections to the region of the LC originating from the VTA. Kainic acid (KA) stimulation of the VTA resulted in a dose-dependent increase in the levels of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) in the prefrontal cortex, and also elevated levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenolglycol (MHPG). Prefrontal cortical MHPG levels did not increase in response to vehicle injection or KA infusion into the hippocampus, nor did concentrations of this metabolite increase in the prefrontal cortex in response to intra-VTA KA in animals with neurotoxic lesions of the VTA. KA injection into the VTA resulted in increased MHPG levels in the hippocampus, but not the hypothalamus. Dorsal noradrenergic bundle knife cuts prevented the KA-elicited prefrontal cortical MHPG increase. These data suggest that stimulation of the mesocoeruleo dopaminergic projection arising from the VTA results in selective excitation of the LC-derived dorsal bundle noradrenergic system.