Research Report Glycine stimulates the release of labeled acetylcholine but not dopamine nor glutamate from superfused rat striatal tissue Marina Sorrentino Hernandes, Leandro de Magalhães, Lanfranco Ranieri Paolo Troncone ⁎ Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503.900, Brazil ARTICLE INFO ABSTRACT Article history: Accepted 20 June 2007 Available online 27 July 2007 Glycine is known as an inhibitory neurotransmitter in the spinal cord and forebrain but its precise role in the forebrain is largely overlooked. This investigation evaluated whether glycine alters acetylcholine, glutamate or dopamine release from striatal tissue using an in vitro approach. We observed that while glycine induced a robust 3 H-acetylcholine release ( 3 H-ACh) from superfused striatal tissue, it failed at releasing 3 H-glutamate or 3 H-dopamine. Glycine stimulated 3 H-ACh release in a dose- and calcium-dependent manner (EC 50 =69 μM). Tetrodotoxin (1 μM) inhibited about 75% of the release demonstrating a predominant dendritic and cell body location of glycine receptors. The prototypical glycine receptor antagonist strychnine at 10 μM completely abolished 3 H-ACh release. To further characterize the role of striatal glycine receptors in 3 H-ACh release we examined glycine effects after in vivo treatment with Haloperidol-decanoate (HD). Treatment for 30 days or more with HD decreased maximal glycine-stimulated release of 3 H-ACh suggesting a non-competitive inhibition. After 30 days of washout release parameters did not return to vehicle-treated levels. The glutamate agonist NMDA also stimulated acetylcholine release but showed slightly different behavior in HD-treated striatal tissue. These effects could be attributed to changes in chloride transporters expressed in the giant striatal cholinergic cell as well as glycine receptor subunit composition and finally, GABA/glycine co-release in this tissue. © 2007 Elsevier B.V. All rights reserved. Keywords: Glycine Striatum Superfusion Neurotransmitter release Acetylcholine Parkinson 1. Introduction Beyond its role as an inhibitory neurotransmitter in the spinal cord and its co-agonistic role on NMDA glutamate receptors (Aprison and Werman, 1965; Johnson and Ascher, 1987; Trist, 2000; Betz and Laube, 2006), glycine has been reported to stimulate the release of transmitters from brain structures in a strychnine-dependent manner (Darstein et al., 1997). Glycine can stimulate dopamine release from striatal tissue (Giorguieff- Chesselet et al., 1979) and substantia nigra (Kerwin and Pycock, 1978) and acetylcholine from striatal tissue and also from the solitary tract nucleus and amygdala (Dudeck et al., 2003; Talman et al., 1994). The mechanisms involved in the inhibitory or excitatory actions of glycine may result from reversed chloride currents in susceptible neurons (Darstein et al., 2000). The basal ganglia are part of a modulatory neuronal loop involved in the regulation of information flow between the cortex and medullar motor neurons. These nuclei are respon- sible for converging, processing and transferring motor and cognitive information (Tisch et al., 2004). Striatum is the largest structure of the basal ganglia and receives most of their afferent fibers, playing the role of a main processing center of motor information (for a review see: Tepper and Bolam, 2004). Functional studies have revealed strychnine-sensitive glycine BRAIN RESEARCH 1168 (2007) 32 – 37 ⁎ Corresponding author. Fax: +55 11 37267222x2133. E-mail address: ltroncone@butantan.gov.br (L.R.P. Troncone). 0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2007.06.090 available at www.sciencedirect.com www.elsevier.com/locate/brainres