[Tachykininergic neurotransmission in the central nervous system]

Tachykinins are widely distributed in mammalian central nervous system and exert a variety of actions through individual specific receptors. Neurotransmitter functions of substance P (SP), a member of mammalian tachykinins, have been firmly established in the spinal cord; SP is highly concentrated in the superficial layers of the dorsal horn, is released upon electrical stimulation, produces a slow excitatory postsynaptic potential in second-order neurons and is inactivated by peptidases. Since SP is contained in unmyelinated primary afferent fibers, which mediate nociception, SP is thought to transmit nociceptive information and contribute to occurrence of pathological pain states such as inflammation and nerve injury. Based on these findings, great effort has been devoted to developing NK-1 tachykinin receptor antagonists as a potent antinociceptive drug, but up to the present such effective drugs are unavailable. Tachykinin receptor antagonists have been also attracting much attention as a novel therapeutic drug for anxiety and depression other than pain. The amygdala, a key brain structure associated with emotional responses, is thought to be a target of tachykinin receptor antagonists for exerting psychopharmacological actions. Indeed, tachykinins enhance inhibitory synaptic transmission in the basolateral complex of the amygdala. Further study of tachykininergic transmission in the central nervous systems will open novel fields for pharmacology and therapeutics in neuropsychiatric disorders.