Substance P (SP) has been implicated in learning and memory processes. This peptide facilitated learning when injected peripherally or directly into the ventral pallidum. SP has high affinity for neurokinin-1 (NK-1) receptors. WIN51,708 is a potent NK-1 receptor antagonist that can inhibit the physiological effects of SP. Immunohistochemical experiments showed that the globus pallidus (GP) and the amygdaloid (AMY) body are rich in SP immunoreactive elements. Pallidal lesions cause learning deficits in active and passive avoidance paradigms. Serious memory deficits develop after lesions of AMY and its role in conditioned fear has been suggested. The aim of our study was to examine whether the SP microinjected into the GP or central nucleus of AMY (ACE) can modify negative reinforcement. Male Wistar rats were conditioned in a passive avoidance situation. Animals were microinjected with 0.4 microl of 10 ng SP, 100 ng SP or vehicle solution into the GP or the ACE. Results showed that 10 ng SP significantly enhanced passive avoidance learning in both structures, while 100 ng SP was ineffective. Retention examined 1 week later was diminished in the GP and still significant in the ACE. The possible involvement o NK-1 receptors in the effects of SP microinjected into the ACE was also studied. Prior treatment with WIN51,708 could block the SP effects on passive avoidance paradigm. Our results are the first to demonstrate that SP plays important roles, though in different ways, in learning and memory processes related to the GP and AMY.