Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system

F. J. White, X. T. Hu, X. F. Zhang, Marina Wolf

Research output: Contribution to journalArticle

254 Citations (Scopus)

Abstract

The development of behavioral sensitization during repeated administration of psychomotor stimulants is a well characterized phenomenon which involves alterations in dopaminergic neurotransmission within the mesoaccumbens system. However, recent evidence indicating that both behavioral sensitization and certain of its neuronal correlates can be prevented by excitatory amino acid recaptor antagonists suggests an integral role for glutamate systems in sensitization processes. Therefore, we have determined whether repeated psychomotor stimulant administration can alter responsiveness of the mesoaccumbens dopamine (DA) system to glutamate. After five daily injections of either cocaine (15.0 mg/kg) or d-amphetamine (5.0 mg/kg), rats were subjected to in vivo single cell recording to determine the efficacy of iontophoretically administered glutamate in altering the firing of ventral tegmental area DA neurons and nucleus accumbens neurons. Current- response determinations indicated that the responsiveness of ventral tegmental area DA neurons to glutamate was significantly enhanced in d- amphetamine-treated and cocaine-treated rats in that the neurons entered a state of apparent depolarization block at significantly lower iontophoretic currents. In contrast, nucleus accumbens neurons in psychomotor stimulant- treated rats were significantly less sensitive to the rate-enhancing effects of glutamate. Thus, sensitization appears to be associated with alterations in glutamate transmission at both the origin and termination of the mesoaccumbens DA pathway.

Original languageEnglish (US)
Pages (from-to)445-454
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume273
Issue number1
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Amphetamine
Cocaine
Glutamic Acid
Dopamine
Dextroamphetamine
Ventral Tegmental Area
Dopaminergic Neurons
Nucleus Accumbens
Neurons
Excitatory Amino Acid Antagonists
Synaptic Transmission
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. / White, F. J.; Hu, X. T.; Zhang, X. F.; Wolf, Marina.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 273, No. 1, 01.01.1995, p. 445-454.

Research output: Contribution to journalArticle

@article{0837bc044bed4237859df0bc6c689daa,
title = "Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system",
abstract = "The development of behavioral sensitization during repeated administration of psychomotor stimulants is a well characterized phenomenon which involves alterations in dopaminergic neurotransmission within the mesoaccumbens system. However, recent evidence indicating that both behavioral sensitization and certain of its neuronal correlates can be prevented by excitatory amino acid recaptor antagonists suggests an integral role for glutamate systems in sensitization processes. Therefore, we have determined whether repeated psychomotor stimulant administration can alter responsiveness of the mesoaccumbens dopamine (DA) system to glutamate. After five daily injections of either cocaine (15.0 mg/kg) or d-amphetamine (5.0 mg/kg), rats were subjected to in vivo single cell recording to determine the efficacy of iontophoretically administered glutamate in altering the firing of ventral tegmental area DA neurons and nucleus accumbens neurons. Current- response determinations indicated that the responsiveness of ventral tegmental area DA neurons to glutamate was significantly enhanced in d- amphetamine-treated and cocaine-treated rats in that the neurons entered a state of apparent depolarization block at significantly lower iontophoretic currents. In contrast, nucleus accumbens neurons in psychomotor stimulant- treated rats were significantly less sensitive to the rate-enhancing effects of glutamate. Thus, sensitization appears to be associated with alterations in glutamate transmission at both the origin and termination of the mesoaccumbens DA pathway.",
author = "White, {F. J.} and Hu, {X. T.} and Zhang, {X. F.} and Marina Wolf",
year = "1995",
month = "1",
day = "1",
language = "English (US)",
volume = "273",
pages = "445--454",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "1",

}

TY - JOUR

T1 - Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system

AU - White, F. J.

AU - Hu, X. T.

AU - Zhang, X. F.

AU - Wolf, Marina

PY - 1995/1/1

Y1 - 1995/1/1

N2 - The development of behavioral sensitization during repeated administration of psychomotor stimulants is a well characterized phenomenon which involves alterations in dopaminergic neurotransmission within the mesoaccumbens system. However, recent evidence indicating that both behavioral sensitization and certain of its neuronal correlates can be prevented by excitatory amino acid recaptor antagonists suggests an integral role for glutamate systems in sensitization processes. Therefore, we have determined whether repeated psychomotor stimulant administration can alter responsiveness of the mesoaccumbens dopamine (DA) system to glutamate. After five daily injections of either cocaine (15.0 mg/kg) or d-amphetamine (5.0 mg/kg), rats were subjected to in vivo single cell recording to determine the efficacy of iontophoretically administered glutamate in altering the firing of ventral tegmental area DA neurons and nucleus accumbens neurons. Current- response determinations indicated that the responsiveness of ventral tegmental area DA neurons to glutamate was significantly enhanced in d- amphetamine-treated and cocaine-treated rats in that the neurons entered a state of apparent depolarization block at significantly lower iontophoretic currents. In contrast, nucleus accumbens neurons in psychomotor stimulant- treated rats were significantly less sensitive to the rate-enhancing effects of glutamate. Thus, sensitization appears to be associated with alterations in glutamate transmission at both the origin and termination of the mesoaccumbens DA pathway.

AB - The development of behavioral sensitization during repeated administration of psychomotor stimulants is a well characterized phenomenon which involves alterations in dopaminergic neurotransmission within the mesoaccumbens system. However, recent evidence indicating that both behavioral sensitization and certain of its neuronal correlates can be prevented by excitatory amino acid recaptor antagonists suggests an integral role for glutamate systems in sensitization processes. Therefore, we have determined whether repeated psychomotor stimulant administration can alter responsiveness of the mesoaccumbens dopamine (DA) system to glutamate. After five daily injections of either cocaine (15.0 mg/kg) or d-amphetamine (5.0 mg/kg), rats were subjected to in vivo single cell recording to determine the efficacy of iontophoretically administered glutamate in altering the firing of ventral tegmental area DA neurons and nucleus accumbens neurons. Current- response determinations indicated that the responsiveness of ventral tegmental area DA neurons to glutamate was significantly enhanced in d- amphetamine-treated and cocaine-treated rats in that the neurons entered a state of apparent depolarization block at significantly lower iontophoretic currents. In contrast, nucleus accumbens neurons in psychomotor stimulant- treated rats were significantly less sensitive to the rate-enhancing effects of glutamate. Thus, sensitization appears to be associated with alterations in glutamate transmission at both the origin and termination of the mesoaccumbens DA pathway.

UR - http://www.scopus.com/inward/record.url?scp=0028953965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028953965&partnerID=8YFLogxK

M3 - Article

C2 - 7714800

AN - SCOPUS:0028953965

VL - 273

SP - 445

EP - 454

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 1

ER -