Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation

L. J. Almodóvar-FÁBREGAS, O. Segarra, N. Colón, J. G. Dones, M. Mercado, C. A. Mejías-Aponte, R. Vázquez, R. Abreu, E. Vázquez, John Williams, C. A. Jiménez-Rivera

Research output: Contribution to journalArticle

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Abstract

The repeated use of psychostimulants in humans has been associated with progressive enhancement of anxiety, panic attacks, and eventually paranoid psychosis. The appearance of such behaviors has been termed behavioral sensitization, which forms part of the basic pathological mechanisms involved in drug addiction. Psychostimulants act via a circuit involving the ventral tegmental area (VTA), prefrontal cortex (PFC), and nucleus accumbens. The PFC sends glutamatergic projections that activate dopaminergic neurons in the VTA. These projections provide an extremely important excitatory drive necessary for the development of sensitization. The effects of cocaine administration on the response of dopaminergic VTA cells to activation of the PFC have not been reported. Here the effects of acute cocaine administration on VTA cell response to PFC stimulation are examined. Statistical analysis of the changes in spontaneous activity and evoked response revealed a significant decrease in spontaneous activity at 1.0 mg/kg i.v. after cocaine treatment compared to baseline levels. The net effect was an increase in signal-to-noise ratio. Treatment with MK-801 at a dose of 2 mg/kg showed that the excitatory response was, at least partially, NMDA-mediated. Prazosin pretreatment (0.5 mg/kg i.p.) did not prevent a significant decrease in spontaneous activity brought about by cocaine (15 mg/kg, i.p.). Nonetheless, prazosin alone induced a significant decrease in the response to PFC stimulation when compared to baseline. In addition, iontophoretic application of norepinephrine (NE) onto VTA cells revealed that NE potentiated (19.2%), enhanced (26.9%), or suppressed (46.2%) the glutamate-evoked response in VTA cells. The results suggest that a possible role of cocaine in the process of sensitization might be to amplify the PFC-induced excitation at the VTA. Since the iontophoretic release of NE in almost half of the sampled cells produced similar effects to those of cocaine it may suggest a possible NE-mediated mechanism for cocaine actions.

Original languageEnglish (US)
Pages (from-to)157-171
Number of pages15
JournalAnnals of the New York Academy of Sciences
Volume965
StatePublished - 2002

Fingerprint

Ventral Tegmental Area
Prefrontal Cortex
Cocaine
Norepinephrine
Prazosin
Paranoid Disorders
Dizocilpine Maleate
Panic Disorder
Dopaminergic Neurons
Nucleus Accumbens
Signal-To-Noise Ratio
N-Methylaspartate
Stimulation
Cells
Neurons
Substance-Related Disorders
Glutamic Acid
Signal to noise ratio
Statistical methods
Anxiety

Keywords

  • Cocaine
  • Norepinephrine
  • Prazosin
  • Prefrontal cortex
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Almodóvar-FÁBREGAS, L. J., Segarra, O., Colón, N., Dones, J. G., Mercado, M., Mejías-Aponte, C. A., ... Jiménez-Rivera, C. A. (2002). Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation. Annals of the New York Academy of Sciences, 965, 157-171.

Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation. / Almodóvar-FÁBREGAS, L. J.; Segarra, O.; Colón, N.; Dones, J. G.; Mercado, M.; Mejías-Aponte, C. A.; Vázquez, R.; Abreu, R.; Vázquez, E.; Williams, John; Jiménez-Rivera, C. A.

In: Annals of the New York Academy of Sciences, Vol. 965, 2002, p. 157-171.

Research output: Contribution to journalArticle

Almodóvar-FÁBREGAS, LJ, Segarra, O, Colón, N, Dones, JG, Mercado, M, Mejías-Aponte, CA, Vázquez, R, Abreu, R, Vázquez, E, Williams, J & Jiménez-Rivera, CA 2002, 'Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation', Annals of the New York Academy of Sciences, vol. 965, pp. 157-171.
Almodóvar-FÁBREGAS LJ, Segarra O, Colón N, Dones JG, Mercado M, Mejías-Aponte CA et al. Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation. Annals of the New York Academy of Sciences. 2002;965:157-171.
Almodóvar-FÁBREGAS, L. J. ; Segarra, O. ; Colón, N. ; Dones, J. G. ; Mercado, M. ; Mejías-Aponte, C. A. ; Vázquez, R. ; Abreu, R. ; Vázquez, E. ; Williams, John ; Jiménez-Rivera, C. A. / Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation. In: Annals of the New York Academy of Sciences. 2002 ; Vol. 965. pp. 157-171.
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