Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine

Alexander Gomez-A, Amanda M. Fiorenza, Suelen L. Boschen, Adam H. Sugi, Danielle Beckman, Sergio T. Ferreira, Kendall H Lee, Charles D. Blaha, Claudio Da Cunha

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Diazepam is a benzodiazepine receptor agonist with anxiolytic and addictive properties. Although most drugs of abuse increase the level of release of dopamine in the nucleus accumbens, here we show that diazepam not only causes the opposite effect but also prevents amphetamine from enhancing dopamine release. We used 20 min sampling in vivo microdialysis and subsecond fast-scan cyclic voltammetry recordings at carbon-fiber microelectrodes to show that diazepam caused a dose-dependent decrease in the level of tonic and electrically evoked dopamine release in the nucleus accumbens of urethane-anesthetized adult male Swiss mice. In fast-scan cyclic voltammetry assays, dopamine release was evoked by electrical stimulation of the ventral tegmental area. We observed that 2 and 3 mg of diazepam/kg reduced the level of electrically evoked dopamine release, and this effect was reversed by administration of the benzodiazepine receptor antagonist flumazenil in doses of 2.5 and 5 mg/kg, respectively. No significant effects on measures of dopamine re-uptake were observed. Cyclic voltammetry experiments further showed that amphetamine (5 mg/kg, intraperitoneally) caused a significant increase in the level of dopamine release and in the half-life for dopamine re-uptake. Diazepam (2 mg/kg) significantly weakened the effect of amphetamine on dopamine release without affecting dopamine re-uptake. These results suggest that the pharmacological effects of benzodiazepines have a dopaminergic component. In addition, our findings challenge the classic view that all drugs of abuse cause dopamine release in the nucleus accumbens and suggest that benzodiazepines could be useful in the treatment of addiction to other drugs that increase the level of dopamine release, such as cocaine, amphetamines, and nicotine.

Original languageEnglish (US)
Pages (from-to)300-309
Number of pages10
JournalACS Chemical Neuroscience
Volume8
Issue number2
DOIs
StatePublished - Feb 15 2017

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Nucleus Accumbens
Amphetamine
Diazepam
Dopamine
Cyclic voltammetry
Street Drugs
GABA-A Receptors
Benzodiazepines
Amphetamines
Flumazenil
Dopamine Agents
Ventral Tegmental Area
Urethane
Anti-Anxiety Agents
Microdialysis
Microelectrodes
Nicotine
Cocaine
Electric Stimulation
Half-Life

Keywords

  • Anticonvulsant
  • Anxiolytic
  • Dopaminergic neurons
  • Electrochemistry
  • GABA
  • Nucleus accumbens core
  • Ventral tegmental area

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Cognitive Neuroscience
  • Cell Biology

Cite this

Gomez-A, A., Fiorenza, A. M., Boschen, S. L., Sugi, A. H., Beckman, D., Ferreira, S. T., ... Da Cunha, C. (2017). Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine. ACS Chemical Neuroscience, 8(2), 300-309. https://doi.org/10.1021/acschemneuro.6b00358

Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine. / Gomez-A, Alexander; Fiorenza, Amanda M.; Boschen, Suelen L.; Sugi, Adam H.; Beckman, Danielle; Ferreira, Sergio T.; Lee, Kendall H; Blaha, Charles D.; Da Cunha, Claudio.

In: ACS Chemical Neuroscience, Vol. 8, No. 2, 15.02.2017, p. 300-309.

Research output: Contribution to journalArticle

Gomez-A, A, Fiorenza, AM, Boschen, SL, Sugi, AH, Beckman, D, Ferreira, ST, Lee, KH, Blaha, CD & Da Cunha, C 2017, 'Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine', ACS Chemical Neuroscience, vol. 8, no. 2, pp. 300-309. https://doi.org/10.1021/acschemneuro.6b00358
Gomez-A, Alexander ; Fiorenza, Amanda M. ; Boschen, Suelen L. ; Sugi, Adam H. ; Beckman, Danielle ; Ferreira, Sergio T. ; Lee, Kendall H ; Blaha, Charles D. ; Da Cunha, Claudio. / Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine. In: ACS Chemical Neuroscience. 2017 ; Vol. 8, No. 2. pp. 300-309.
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