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

✍ Scribed by Elvira Galarraga; Salvador Hernández-López; Dagoberto Tapia; Arturo Reyes; José Bargas

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 243 KB
• Volume: 33
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199907)33:1<26::aid-syn3>3.0.co;2-4

✦ Synopsis

Substance P (SP) acts as a neurotransmitter in the neostriatum through the axon collaterals of spiny projection neurons. However, possible direct or indirect actions of SP on the neostriatal output neurons have not been described. 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 both DA and ACh on spiny neurons are known, we asked if activation of neostriatal NK 1 -class receptors is able to reproduce them. The SP NK 1 -receptor agonist, GR73632 (1 µM), had both excitatory and inhibitory actions on virtually all spiny neurons tested at resting potential. The excitatory action was blocked by atropine and coursed with an increase in firing rate and input resistance (R N ). The inhibitory action was blocked by haloperidol and coursed with a reduction in firing rate and R N . Therefore, the release of both DA and ACh induced by NK 1 -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 R N that accompanied this response could be observed in the presence of 1 µM TTX or 100 µM Cd 2ϩ , suggesting a direct effect. Double labeling showed that only SP-immunoreactive neurons were facilitated by NK 1receptor activation in these conditions.