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Increased spontaneous activity following substance P infusion into A10 dopaminergic area


THE polypeptide, substance P, has a discrete regional distribution in mammalian CNS; particularly high concentrations are found in the mesencephalon, close to the origin of the two major ascending dopaminergic pathways1,2. Two further observations which may reflect functional neurotransmission are, first, that substance P is released from spinal cord and hypothalamus3,4, and second, that it has been localised using fragmentation techniques in nerve ending particles of bovine hypothalamus and substantia nigra5,6. Further support for this hypothesis comes from iontophoretic studies in which application of substance P into the medial nucleus of amygdala and substantia nigra induced a strong neuronal activation7,8. It has also been shown biochemically that the activity of dopaminergic systems may be modulated by substance P neurones9,0. The ventral tegmental area (VTA), which contains the cell bodies of the dopaminergic A10 neurones (DA-A10), receives a substance P innervation mainly from substance P cell bodies localised in the medial habenular nucleus11,12. DA-A10 neurones give rise to the mesolimbic DA system and also to the mesocortical DA axons innervating cerebral cortical area13,14. We have studied the behavioural effects of local application of substance P into the VTA, to try to elucidate the physiological role of substance P innervation of this area. A strong enhancement of spontaneous activity was observed following bilateral infusion of substance P. A major feature of this enhancement was increased exploratory behaviour. Moreover d-amphetamine-induced behavioural arousal was potentiated by previous infusion (1 h) of substance P into the VTA.

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STINUS, L., KELLEY, A. & IVERSEN, S. Increased spontaneous activity following substance P infusion into A10 dopaminergic area. Nature 276, 616–618 (1978).

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