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Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms.

Abstract：

:Substance P (SP) is an undecapeptide that is co-localized with conventional transmitters in the nucleus accumbens (NAc). Its neurochemical and behavioral effects resemble those of cocaine and amphetamine. How SP accomplishes these effects is not known, partly because its cellular and synaptic effects are not well characterized. Using whole cell and nystatin-perforated patch recording in rat forebrain slices, we show here that SP, an excitatory neuropeptide, depresses evoked excitatory postsynaptic currents (EPSCs) and potentials (EPSPs) in NAc through intermediate neuromodulators. SP caused a partially reversible, dose-dependent decrease in evoked EPSCs. This effect was mimicked by a neurokinin-1 (NK1) receptor-selective agonist, [Sar(9), Met (O(2))(11)]-SP and blocked by a NK1 receptor-selective antagonist, L 732 138. Both the SP- and [Sar(9), Met (O(2))(11)]-SP-induced synaptic depressions were accompanied by increases in paired pulse ratio (PPR), effects that were also blocked by L 732 138. In contrast to its effect on PPR, SP did not produce significant changes in the holding current, input resistance, EPSC decay rate (tau), and steady-state I-V curves of the recorded cells. The SP-induced synaptic depressions were prevented by dopamine receptor blockade using SCH23390 and haloperidol, but not by sulpiride. In addition, the SP-induced synaptic depression was blocked by an adenosine A1 receptor blocker 8-cyclopentyltheophylline (8-CPT) but not the N-methyl-D-aspartate (NMDA) receptor antagonist D-APV. These data show that SP, by activating presynaptic NK1 receptors, depresses excitatory synaptic transmission indirectly by enhancing extracellular dopamine and adenosine levels. Since the cellular and synaptic effects of SP resemble those of cocaine and amphetamine, it may serve as an endogenous psychogenic peptide.

journal_name

J Neurophysiol

journal_title

Journal of neurophysiology

authors

Kombian SB,Ananthalakshmi KV,Parvathy SS,Matowe WC

doi

10.1152/jn.00854.2002

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

728-37

issue

eissn

0022-3077

issn

1522-1598

journal_volume

pub_type

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Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms.