There is increasing evidence that kainate receptors contribute to both postsynaptic and presynaptic signaling not only in the hippocampus but also in the amygdala. The present study demonstrates that low concentrations of the specific kainate GLU_K5 receptor agonist, ATPA, depressed baseline activity in the lateral nucleus of the rat amygdala (LA), induced by stimulation of external capsule fibers or by intranuclear stimulation in horizontal brain slices. ATPA reduced high-frequency-induced long-term potentiation (LTP) in males while it enhanced LTP in females during certain phases of the estrus cycle. In untreated slices from females, LA-LTP differed depending on the phase of the estrus cycle. In addition, we show for the first time that the p38 mitogen-activated protein (MAP) kinase inhibitor, SKF 86002, reduced LA-LTP. In males, the effects of ATPA and SKF 86002 were not additive. To the contrary, in females, the exposure to ATPA in control plus SKF 86002 increases LTP relative to control plus SKF 86002 alone. Thus, we demonstrate that the effectiveness of GLU_K5 stimulation on plasticity changes in the amygdala is gender-dependent and that the MAP kinase pathway might be involved in males.–Schubert, M., Drephal, C., Albrecht, D. Gender-dependent ATPA-induced changes in long-term potentiation in the rat lateral amygdala.