Substance P, neurotensin and enkephalin injections into the ventral tegmental area: comparative study on dopamine turnover in several forebrain structures

doi:10.1016/0006-8993(89)90523-4

Brain Research

Volume 486, Issue 2, 8 May 1989, Pages 357-363

https://doi.org/10.1016/0006-8993(89)90523-4 Get rights and content

Abstract

A comparison of dopaminergic (DAergic) turnover changes in several forebrain structures was investigated after local injection of substance P (SP), neurotensin andD-Ala-Met-enkephalin (DALA) into the ventral tegmental area (VTA). A dose-dependent increase in the DOPAC/DA ratio was elicited by all 3 peptides in the nucleus accumbens and the septum. DAergic turnover was enhanced in the anteromedial prefrontal cortex only after SP injection and in the amygdala only after neurotensin injection. In the anteromedial striatum as well as in the posterolateral striatum, a significant increased DOPAC/DA ratio was observed following SP and DALA injection into the VTA. No significant changes were noticed in the olfactory tubercles after injection of the 3 peptides in the VTA. From these results, it appears that each peptide induced a different profile of DAergic activation. Taking into account the facilitatory role of the DA neurons at the level of the forebrain integrative structures, the differential activation may explain the difference in behavioral response obtained after injection of the 3 peptides in the VTA.

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Identifying endogenous substances with such an action will improve our understanding of the development of addiction and may lead to new targets or therapeutic options for substance abuse treatment and related psychiatric disorders. In this regard, SP has been reported to increase extracellular dopamine concentration in the NAc (Boix et al., 1992a,b; Cador et al., 1989; Placenza et al., 2004) and also shown to utilize dopamine as an intermediate to depress EPSCs in the NAc (Kombian et al., 2003). Furthermore, this effect of SP was reported to occlude the actions of cocaine (Kombian et al., 2009).
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Accumulating evidence suggests that the neuropeptide substance P (SP) and its principal receptor neurokinin 1 (NK1) play a specific role in the behavioral response to opioids and stress that may help to initiate and maintain addictive behavior. In animal models, the NK1 receptor is required for opioids to produce their rewarding and motivational effects. SP neurotransmission is also implicated in the behavioral response to stress and in the process of drug sensitization, potentially contributing to vulnerability to addiction or relapse. However, SP neurotransmission only plays a minor role in opioid-mediated antinociception and the development of opioid tolerance. Moreover, the effects of SP on addiction-related behavior are selective for opioids and evidence supporting a role in the response to cocaine or psychostimulants is less compelling. This review will summarize the effects of SP neurotransmission on opioid-dependent behaviors and correlate them with potential contributing neural pathways. Specifically, SP neurotransmission within components of the basal forebrain particularly the nucleus accumbens and ventral pallidum as well as actions within the ascending serotonin system will be emphasized. In addition, cellular- or network-level interactions between opioids and SP signaling that may underlie the specificity of their relationship will be reviewed.
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Substance P, neurotensin and enkephalin injections into the ventral tegmental area: comparative study on dopamine turnover in several forebrain structures

Abstract

Neuropharmacology

Neuroscience

Peptides

Brain Research

Brain Research

Brain Research

Pharmacol. Biochem. Behav.

Life Sci.

Brain Research

Brain Research

J. Neurosci. Meth.

Int. Rev. Neurobiol.

Brain Res. Bull.

A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines

J. Pharmacol. Exp. Ther.

Role of endogenous substance P in stress-induced activation of mesocortical dopamine neurones

Nature (Lond.)

Dopamine containing systems in the CNS

Stimulant effects of enkephalin microinjection into the dopaminergic A10 area

Nature (Lond.)