Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington's disease

Isabel Lastres-Becker, Filomena Fezza, Maribel Cebeira, Tiziana Bisogno, José A. Ramos, Alfredo Milone, Javier Fernández-Ruiz, Vincenzo Di Marzo

Research output: Contribution to journalArticle

Abstract

Recent studies have demonstrated a loss of cannabinoid CB1 receptors in the basal ganglia in Huntington's disease (HD), but there are no data on endocannabinoid levels in this disease. In the present study, we have addressed this question by using rats with bilateral intrastriatal injections of 3-nitropropionic acid (3-NP), a toxin that, through the selective damage of striatal GABAergic efferent neurons, produces a useful model of HD. Twelve days after the lesion, 3-NP-lesioned rats exhibited motor disturbances, characterized by an ambulatory hyperactivity accompanied by a loss of guided activities. Analysis of GABA contents in the basal ganglia showed a trend towards a reduction compatible with motor hyperactivity. In addition, CB1 receptor binding and, to a greater extent, CB1 receptor activation of GTP-binding proteins, were also reduced in the basal ganglia. These changes were paralleled by a decrease of the contents of the two endocannabinoids, anandamide and 2-arachidonoylglycerol, in the striatum, and by an increase, particularly of anandamide, in the ventral mesencephalon where the substantia nigra is located. Both CB1 receptors and endocannabinoid levels were not altered in the cerebral cortex, an area not affected by the lesion. In summary, behavioral and biochemical changes observed in rats intrastriatally lesioned with 3-NP were similar to those occurring in the brain of HD patients. As expected, a loss of CB1 receptor function was evident in the basal ganglia of these rats and this was accompanied by different changes in endocannabinoid levels.

Original languageEnglish
Pages (from-to)2125-2129
Number of pages5
JournalNeuroReport
Volume12
Issue number10
Publication statusPublished - Jul 20 2001

Keywords

  • 3-Nitropropionic acid
  • Basal ganglia
  • CB receptors
  • Endocannabinoids
  • GABA
  • Huntington's disease

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Lastres-Becker, I., Fezza, F., Cebeira, M., Bisogno, T., Ramos, J. A., Milone, A., Fernández-Ruiz, J., & Marzo, V. D. (2001). Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington's disease. NeuroReport, 12(10), 2125-2129.