QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 15, 2004, 24(50):11449-11456; doi:10.1523/JNEUROSCI.3597-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (35) Citing Articles via Google Scholar Google Scholar Articles by Mark, K. A. Articles by Yamamoto, B. K. Search for Related Content PubMed PubMed Citation Articles by Mark, K. A. Articles by Yamamoto, B. K.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
High-Dose Methamphetamine Acutely Activates the Striatonigral Pathway to Increase Striatal Glutamate and Mediate Long-Term Dopamine Toxicity

Karla A. Mark,¹ Jean-Jacques Soghomonian,² and Bryan K. Yamamoto¹

¹Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics, and ²Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118

Methamphetamine (METH) has been shown to increase the extracellular concentrations of both dopamine (DA) and glutamate (GLU) in the striatum. Dopamine, glutamate, or their combined effects have been hypothesized to mediate striatal DA nerve terminal damage. Although it is known that METH releases DA via reverse transport, it is not known how METH increases the release of GLU. We hypothesized that METH increases GLU indirectly via activation of the basal ganglia output pathways. METH increased striatonigral GABAergic transmission, as evidenced by increased striatal GAD65 mRNA expression and extracellular GABA concentrations in substantia nigra pars reticulata (SNr). The METH-induced increase in nigral extracellular GABA concentrations was D1 receptor-dependent because intranigral perfusion of the D1 DA antagonist SCH23390(10 µM) attenuated the METH-induced increase in GABA release in the SNr. Additionally, METH decreased extracellular GABA concentrations in the ventromedial thalamus (VM). Intranigral perfusion of the GABA-A receptor antagonist, bicuculline (10 µM), blocked the METH-induced decrease in extracellular GABA in the VM and the METH-induced increase in striatal GLU. Intranigral perfusion of either a DA D1 or GABA-A receptor antagonist during the systemic administrations of METH attenuated the striatal DA depletions when measured 1 week later. These results show that METH enhances D1-mediated striatonigral GABAergic transmission (1), which in turn activates GABA-A receptors in the SNr (2), leading to a decrease in GABAergic nigrothalamic activity (3), an increase in corticostriatal GLU release (4), and a consequent long-term depletion of striatal DA content (5).

Key words: GABA; D1; GABA-A; substantia nigra; thalamus; microdialysis

---

Received Sep 1, 2004; revised November 12, 2004; accepted November 13, 2004.

This article has been cited by other articles:

				G. C. Hadlock, A. J. Baucum II, J. L. King, K. A. Horner, G. A. Cook, J. W. Gibb, D. G. Wilkins, G. R. Hanson, and A. E. Fleckenstein Mechanisms Underlying Methamphetamine-Induced Dopamine Transporter Complex Formation J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 169 - 174. [Abstract] [Full Text] [PDF]

				H. A. Boger, L. D. Middaugh, K. S. Patrick, S. Ramamoorthy, E. D. Denehy, H. Zhu, A. M. Pacchioni, A.-C. Granholm, and J. F. McGinty Long-Term Consequences of Methamphetamine Exposure in Young Adults Are Exacerbated in Glial Cell Line-Derived Neurotrophic Factor Heterozygous Mice J. Neurosci., August 15, 2007; 27(33): 8816 - 8825. [Abstract] [Full Text] [PDF]

				K. A. Mark, M. S. Quinton, S. J. Russek, and B. K. Yamamoto Dynamic Changes in Vesicular Glutamate Transporter 1 Function and Expression Related to Methamphetamine-Induced Glutamate Release J. Neurosci., June 20, 2007; 27(25): 6823 - 6831. [Abstract] [Full Text] [PDF]

				T. Hatzipetros, J. G. Raudensky, J.-J. Soghomonian, and B. K. Yamamoto Haloperidol Treatment after High-Dose Methamphetamine Administration Is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata J. Neurosci., May 30, 2007; 27(22): 5895 - 5902. [Abstract] [Full Text] [PDF]

				M. Marti, C. Trapella, R. Viaro, and M. Morari The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and L-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway J. Neurosci., February 7, 2007; 27(6): 1297 - 1307. [Abstract] [Full Text] [PDF]

				K. A. Horner, S. C. Westwood, G. R. Hanson, and K. A. Keefe Multiple High Doses of Methamphetamine Increase the Number of Preproneuropeptide Y mRNA-Expressing Neurons in the Striatum of Rat via a Dopamine D1 Receptor-Dependent Mechanism J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 414 - 421. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help