Increased responsiveness of ventral tegmental area dopamine neurons to glutamate after repeated administration of cocaine or amphetamine is transient and selectively involves AMPA receptors

Xu Feng Zhang, Xiu Ti Hu, Francis J. White, Marina Wolf

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Abstract

It is well established that behavioral sensitization to psychomotor stimulants is associated with adaptations in the mesoaccumbens dopamine (DA) system. We showed previously that the responsiveness of ventral tegmental area (VTA) DA neurons to glutamate was significantly enhanced in amphetamine- and cocaine-pretreated rats tested after 3 days of withdrawal, which suggests that adaptations in excitatory amine acid transmission also contribute to sensitization. The purpose of the present study was to determine the subtype of excitatory amine acid receptor responsible for this effect and to examine its persistence during withdrawal. Extracellular single cell recording and microiontophoresis were used to investigate possible alterations in the ability of glutamate agonists [(S)-α-amino-3-hydroxy-5- methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate (NMDA), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-t-ACPD)] to stimulate the firing of VTADA neurons after 3 days of withdrawal from repeated administration of saline, cocaine or amphetamine. Current-response curves showed that responses to iontophoretic AMPA, but not NMDA or 1S,3R-t- ACPD were significantly enhanced in cocaine- or amphetamine-pretreated rats in that neurons entered into a state of apparent depolarization block at significantly lower iontophoretic currents. When rats were tested for responsiveness to iontophoretic glutamate after 14 days of withdrawal, there was no significant difference between cocaine- or amphetamine- and saline- pretreated rats with respect to glutamate current-response curves. These results suggest that increased responsiveness of AMPA receptors on VTA DA neurons may contribute to sensitization at early withdrawal times, but that this alteration, like others described within the VTA, is transient.

Original languageEnglish (US)
Pages (from-to)699-706
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume281
Issue number2
StatePublished - May 1 1997
Externally publishedYes

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Ventral Tegmental Area
AMPA Receptors
Dopaminergic Neurons
Amphetamine
Cocaine
Glutamic Acid
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
N-Methylaspartate
Amines
Isoxazoles
Excitatory Amino Acid Agonists
Neurons
Acids
Propionates
Dopamine
1-amino-1,3-dicarboxycyclopentane

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Increased responsiveness of ventral tegmental area dopamine neurons to glutamate after repeated administration of cocaine or amphetamine is transient and selectively involves AMPA receptors",
abstract = "It is well established that behavioral sensitization to psychomotor stimulants is associated with adaptations in the mesoaccumbens dopamine (DA) system. We showed previously that the responsiveness of ventral tegmental area (VTA) DA neurons to glutamate was significantly enhanced in amphetamine- and cocaine-pretreated rats tested after 3 days of withdrawal, which suggests that adaptations in excitatory amine acid transmission also contribute to sensitization. The purpose of the present study was to determine the subtype of excitatory amine acid receptor responsible for this effect and to examine its persistence during withdrawal. Extracellular single cell recording and microiontophoresis were used to investigate possible alterations in the ability of glutamate agonists [(S)-α-amino-3-hydroxy-5- methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate (NMDA), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-t-ACPD)] to stimulate the firing of VTADA neurons after 3 days of withdrawal from repeated administration of saline, cocaine or amphetamine. Current-response curves showed that responses to iontophoretic AMPA, but not NMDA or 1S,3R-t- ACPD were significantly enhanced in cocaine- or amphetamine-pretreated rats in that neurons entered into a state of apparent depolarization block at significantly lower iontophoretic currents. When rats were tested for responsiveness to iontophoretic glutamate after 14 days of withdrawal, there was no significant difference between cocaine- or amphetamine- and saline- pretreated rats with respect to glutamate current-response curves. These results suggest that increased responsiveness of AMPA receptors on VTA DA neurons may contribute to sensitization at early withdrawal times, but that this alteration, like others described within the VTA, is transient.",
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T1 - Increased responsiveness of ventral tegmental area dopamine neurons to glutamate after repeated administration of cocaine or amphetamine is transient and selectively involves AMPA receptors

AU - Zhang, Xu Feng

AU - Hu, Xiu Ti

AU - White, Francis J.

AU - Wolf, Marina

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N2 - It is well established that behavioral sensitization to psychomotor stimulants is associated with adaptations in the mesoaccumbens dopamine (DA) system. We showed previously that the responsiveness of ventral tegmental area (VTA) DA neurons to glutamate was significantly enhanced in amphetamine- and cocaine-pretreated rats tested after 3 days of withdrawal, which suggests that adaptations in excitatory amine acid transmission also contribute to sensitization. The purpose of the present study was to determine the subtype of excitatory amine acid receptor responsible for this effect and to examine its persistence during withdrawal. Extracellular single cell recording and microiontophoresis were used to investigate possible alterations in the ability of glutamate agonists [(S)-α-amino-3-hydroxy-5- methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate (NMDA), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-t-ACPD)] to stimulate the firing of VTADA neurons after 3 days of withdrawal from repeated administration of saline, cocaine or amphetamine. Current-response curves showed that responses to iontophoretic AMPA, but not NMDA or 1S,3R-t- ACPD were significantly enhanced in cocaine- or amphetamine-pretreated rats in that neurons entered into a state of apparent depolarization block at significantly lower iontophoretic currents. When rats were tested for responsiveness to iontophoretic glutamate after 14 days of withdrawal, there was no significant difference between cocaine- or amphetamine- and saline- pretreated rats with respect to glutamate current-response curves. These results suggest that increased responsiveness of AMPA receptors on VTA DA neurons may contribute to sensitization at early withdrawal times, but that this alteration, like others described within the VTA, is transient.

AB - It is well established that behavioral sensitization to psychomotor stimulants is associated with adaptations in the mesoaccumbens dopamine (DA) system. We showed previously that the responsiveness of ventral tegmental area (VTA) DA neurons to glutamate was significantly enhanced in amphetamine- and cocaine-pretreated rats tested after 3 days of withdrawal, which suggests that adaptations in excitatory amine acid transmission also contribute to sensitization. The purpose of the present study was to determine the subtype of excitatory amine acid receptor responsible for this effect and to examine its persistence during withdrawal. Extracellular single cell recording and microiontophoresis were used to investigate possible alterations in the ability of glutamate agonists [(S)-α-amino-3-hydroxy-5- methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate (NMDA), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-t-ACPD)] to stimulate the firing of VTADA neurons after 3 days of withdrawal from repeated administration of saline, cocaine or amphetamine. Current-response curves showed that responses to iontophoretic AMPA, but not NMDA or 1S,3R-t- ACPD were significantly enhanced in cocaine- or amphetamine-pretreated rats in that neurons entered into a state of apparent depolarization block at significantly lower iontophoretic currents. When rats were tested for responsiveness to iontophoretic glutamate after 14 days of withdrawal, there was no significant difference between cocaine- or amphetamine- and saline- pretreated rats with respect to glutamate current-response curves. These results suggest that increased responsiveness of AMPA receptors on VTA DA neurons may contribute to sensitization at early withdrawal times, but that this alteration, like others described within the VTA, is transient.

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