Action of substance P (neurokinin-1) receptor activation on rat neostriatal projection neurons

Substance P (SP) acts as a neurotransmitter in the neostriatum through the axon collaterals of spiny projection neurons. However, possible direct or i ndirect actions of SP on the neostriatal output neurons have not been descr ibed. Targets of SP terminals within the neostriatum include interneurons, spiny neurons, afferent fibers and boutons. SP induces the release of both dopamine (DA) and acetylcholine (ACh). Since some postsynaptic actions of b oth DA and ACh on spiny neurons are known, we asked if activation of neostr iatal NK1-class receptors is able to reproduce them. The SP NK1-receptor ag onist, GR73632 (1 mu M), had both excitatory and inhibitory actions on virt ually all spiny neurons tested at resting potential. The excitatory action was blocked by atropine and coursed with an increase in firing rate and inp ut resistance (R-N). The inhibitory action was blocked by haloperidol and c oursed with a reduction in firing rate and R-N. Therefore, the release of b oth DA and ACh induced by NK1-receptor activation modulates indirectly the excitability of the projection neurons. SP facilitates the actions of these transmitters on the spiny neuron. A residual excitatory response to the NK 1-receptor agonist was observed in 30% of a sample of neurons tested in the presence of both haloperidol and atropine. The increase in RN that accompa nied this response could be observed in the presence of 1 mu M TTX or 100 m u M Cd2+, suggesting a direct effect. Double labeling showed that only SP-i mmunoreactive neurons were facilitated by NK1-receptor activation in these conditions. Synapse 33:26-35, 1999. (C) 1999 Wiley-Liss, Inc.