Local injection of a glutamate uptake inhibitor into the ventral tegmental area produces sensitization to the behavioural effects of d-amphetamine

Aked, Joseph; Coizet, Véronique; Clark, David; Overton, Paul G.

doi:10.1016/j.neuroscience.2005.04.044

Cited by 7 publications

(6 citation statements)

References 24 publications

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“…This dual action of AMPH predicts that EAAT3 downregulation will underlie some of the behavioral effects of AMPH and is consistent with previous findings implicating glutamate transporters in AMPH-mediated behaviors. For example, sensitization to AMPH is enhanced by blocking glutamate transporters (Aked et al, 2005) while acute responses (Rasmussen et al, 2011) and reinforcing effects (Fujio et al, 2005; Rawls et al, 2008) of AMPH are attenuated by increasing the expression of glutamate transporters.These data underscore the importance of glutamate transporters and the processes that govern their activity to the behavioral responses to AMPH.…”

Section: Discussionmentioning

confidence: 99%

Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

Underhill

Wheeler

et al. 2014

Neuron

102

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Summary Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons in vitro and in vivo. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C-terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization and its action on excitatory responses. These data indicate that the internalization of EAAT3 triggered by amphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

Underhill

Wheeler

et al. 2014

Neuron

102

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“…Ibotenate lesions of the mPFC prevent amphetamine from increasing VTA glutamate levels (Wolf and Xue, 1999). In addition, repeated injections of the glutamate uptake inhibitor L-trans-pyrollidine-2,4-dicarboxylic acid into the VTA induced behavioral sensitization to amphetamine, an effect blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (Aked et al, 2005). Thus, repeated increases in glutamate levels in the VTA seem to be capable of inducing a sensitized behavioral response to amphetamine or cocaine.…”

Section: Neurochemistry/neuropharmacologymentioning

confidence: 99%

Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior

2011

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“…At least some degree of cross-sensitization exists between cocaine and glutamate because NMDA or AMPA receptor agonist administration produces a sensitized behavioral response in rats previously exposed to cocaine (Bell and Kalivas, 1996; Pierce et al, 1996). Related experiments have demonstrated that a single injection of amphetamine induces behavioral sensitization in rats exposed previously to glutamate itself or to pharmacological agents that increase extracellular glutamate (Aked et al, 2005). Taken together, these results indicate that the ability of cocaine to produce sensitized behavioral responses in mammals is highly dependent on increased glutamate signaling.…”

Section: Introductionmentioning

confidence: 99%

First evidence that drugs of abuse produce behavioral sensitization and cross sensitization in planarians

Rawls¹,

Patil²,

Yuvasheva³

et al. 2010

Behavioural Pharmacology

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Behavioral sensitization in mammals, including humans, is sensitive to factors such as administration route, testing environment, and pharmacokinetic confounds, unrelated to the drugs themselves, that are difficult to eliminate. Simpler animals less susceptible to these confounding influences may be advantageous substitutes for studying sensitization. We tested this hypothesis by determining if planarians display sensitization and cross-sensitization to cocaine and glutamate. Planarian hyperactivity was quantified as the number of C-like hyperkinesias during a 1-min drug exposure. Planarians exposed initially to cocaine (or glutamate) on day 1 were challenged with cocaine (or glutamate) after 2 or 6 days of abstinence. Acute cocaine or glutamate produced concentration-related hyperactivity. Cocaine or glutamate challenge after 2 and 6 days of abstinence enhanced the hyperactivity, indicating the substances produced planarian behavioral sensitization (pBS). Cross-sensitization experiments showed that cocaine produced greater hyperactivity in planarians previously exposed to glutamate than in glutamate-naïve planarians, and vice versa. Behavioral responses were pharmacologically selective because neither scopolamine nor caffeine produced pBS despite causing hyperactivity after initial administration, and acute GABA did not cause hyperactivity. Demonstration of pharmacologically-selective behavioral sensitization in planarians suggests these flatworms represent a sensitive in vivo model to study cocaine behavioral sensitization and to screen potential abuse-deterrent therapeutics.

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Local injection of a glutamate uptake inhibitor into the ventral tegmental area produces sensitization to the behavioural effects of d-amphetamine

Cited by 7 publications

References 24 publications

Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior

First evidence that drugs of abuse produce behavioral sensitization and cross sensitization in planarians

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