Substance P stimulates inhibitory synaptic transmission in the guinea pig basolateral amygdala in vitro

To determine the physiological role of tachykinin NK1 receptors in the basolateral nucleus of the amygdala (BLN) we have studied the electrophysiological effects of substance P (SP) in the absence and presence of selective tachykinin receptor antagonists in guinea pig brain slices. Recordings were made from two populations of neurones; spiny pyramidal and stellate neurones, both thought to be projection neurones. Activation of NK1 receptors with SP increased the frequency of spontaneous inhibitory postsynaptic potentials in the majority of cells. This effect was blocked by bicuculline or tetrodotoxin, but not ionotropic glutamate receptor antagonists. The enhanced synaptic activity induced by SP was antagonised by the NK1 receptor antagonist L-760,735 but not by the less active enantiomer L-781,773 or the NK3 receptor antagonist L-769,927. Thus in the basolateral nucleus of the guinea pig amygdala, NK1 receptor activation preferentially stimulates inhibitory synaptic activity. Consistent with this observation, immunohistochemistry revealed NK1 receptor immunoreactivity to be largely restricted to a subset of GABA interneurones. These studies support a physiological role for SP in the regulation of pathways involved in the control of emotional behaviour.