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Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area.
Life Sci. 2005 Jun 24; 77(6):635-49.LS

Abstract

Behavioral and neurochemical studies suggest that the induction of behavioral sensitization to psychostimulants involves transient changes at the synapses of the ventral tegmental area's dopaminergic neurons (VTA-DA). Differences in the behavioral response to amphetamine (Amph) and methylphenidate (MPD) were observed. In an attempt to understand these behavioral differences at the neuronal level, the dose-response characteristics of these two psychostimulants on electrophysiologically identified VTA-DA neurons at the glutamatergic synapse were investigated. Miniature excitatory post-synaptic currents (mEPSCs) and electrically induced EPSCs were recorded from horizontal midbrain slices of rats that had been pretreated intraperitoneally (i.p.) with saline (control), Amph (2.5, 5.0, 10.0 or 20.0 mg/kg), or MPD (2.5, 5.0, 10.0 or 20.0 mg/kg) 24 h before the recording. Perfusion of Amph through the bath (2.5, 5.0, 10.0 or 20.0 microM) increased the frequency (p<0.01) and the amplitude (p<0.05) of mEPSCs in dose-response characteristics, while MPD perfusion through the bath (2.5, 5.0, 10.0, or 20.0 microM) increased only the frequency (p<0.05) of the mEPSC. Both psychostimulants increased the prefrontal cortex's (PFC) glutamatergic EPSC in the VTA-DA neurons. However, only the higher doses of MPD induced significant effects (p<0.05) on the N-methyl-D-aspartate (NMDA) receptor-mediated EPSC but had no effects on the EPSC mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA/kainate) receptors. Contrarily, Amph increased both kinds of mediated EPSC, but mainly the EPSC mediated by AMPA/kainate receptors (p<0.01). These electrophysiological differences could represent the underlying mechanism responsible for the differences of behavioral effects, such as behavioral sensitization, elicited by MPD and Amph.

Authors+Show Affiliations

Departamento de Fisiologia, Divivion de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Apdo, Postal 70250, Mexico 20, D.F.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15921995

Citation

Prieto-Gómez, B, et al. "Methylphenidate and Amphetamine Modulate Differently the NMDA and AMPA Glutamatergic Transmission of Dopaminergic Neurons in the Ventral Tegmental Area." Life Sciences, vol. 77, no. 6, 2005, pp. 635-49.
Prieto-Gómez B, Vázquez-Alvarez AM, Martínez-Peña JL, et al. Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area. Life Sci. 2005;77(6):635-49.
Prieto-Gómez, B., Vázquez-Alvarez, A. M., Martínez-Peña, J. L., Reyes-Vázquez, C., Yang, P. B., & Dafny, N. (2005). Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area. Life Sciences, 77(6), 635-49.
Prieto-Gómez B, et al. Methylphenidate and Amphetamine Modulate Differently the NMDA and AMPA Glutamatergic Transmission of Dopaminergic Neurons in the Ventral Tegmental Area. Life Sci. 2005 Jun 24;77(6):635-49. PubMed PMID: 15921995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area. AU - Prieto-Gómez,B, AU - Vázquez-Alvarez,A M, AU - Martínez-Peña,J L, AU - Reyes-Vázquez,C, AU - Yang,P B, AU - Dafny,N, PY - 2004/04/27/received PY - 2004/10/27/accepted PY - 2005/6/1/pubmed PY - 2005/7/6/medline PY - 2005/6/1/entrez SP - 635 EP - 49 JF - Life sciences JO - Life Sci. VL - 77 IS - 6 N2 - Behavioral and neurochemical studies suggest that the induction of behavioral sensitization to psychostimulants involves transient changes at the synapses of the ventral tegmental area's dopaminergic neurons (VTA-DA). Differences in the behavioral response to amphetamine (Amph) and methylphenidate (MPD) were observed. In an attempt to understand these behavioral differences at the neuronal level, the dose-response characteristics of these two psychostimulants on electrophysiologically identified VTA-DA neurons at the glutamatergic synapse were investigated. Miniature excitatory post-synaptic currents (mEPSCs) and electrically induced EPSCs were recorded from horizontal midbrain slices of rats that had been pretreated intraperitoneally (i.p.) with saline (control), Amph (2.5, 5.0, 10.0 or 20.0 mg/kg), or MPD (2.5, 5.0, 10.0 or 20.0 mg/kg) 24 h before the recording. Perfusion of Amph through the bath (2.5, 5.0, 10.0 or 20.0 microM) increased the frequency (p<0.01) and the amplitude (p<0.05) of mEPSCs in dose-response characteristics, while MPD perfusion through the bath (2.5, 5.0, 10.0, or 20.0 microM) increased only the frequency (p<0.05) of the mEPSC. Both psychostimulants increased the prefrontal cortex's (PFC) glutamatergic EPSC in the VTA-DA neurons. However, only the higher doses of MPD induced significant effects (p<0.05) on the N-methyl-D-aspartate (NMDA) receptor-mediated EPSC but had no effects on the EPSC mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA/kainate) receptors. Contrarily, Amph increased both kinds of mediated EPSC, but mainly the EPSC mediated by AMPA/kainate receptors (p<0.01). These electrophysiological differences could represent the underlying mechanism responsible for the differences of behavioral effects, such as behavioral sensitization, elicited by MPD and Amph. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/15921995/Methylphenidate_and_amphetamine_modulate_differently_the_NMDA_and_AMPA_glutamatergic_transmission_of_dopaminergic_neurons_in_the_ventral_tegmental_area_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(05)00200-6 DB - PRIME DP - Unbound Medicine ER -