TY - JOUR
T1 - Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain
AU - Hohmann, A. G.
AU - Matsumoto, R. R.
AU - Hemstreet, M. K.
AU - Patrick, S. L.
AU - Margulies, J. E.
AU - Hammer, R. P.
AU - Walker, J. M.
N1 - Funding Information:
Hospital, Providence,R I) for the use of his glucosea nalyzer.W e are grateful for the technical expertise and guidance provided by Dr. Daniel Clew (Department of Anatomy and Reproductive Biology. Universityo f Hawaii, Honolulu, HI) while instructingR RM in experimental procedures. This study was supported by funds from the Dystonia Medical Research Foundation and U.S. Public Health Service (DA-04988 to JMW and DA-06645 to RPH).
PY - 1992/10/16
Y1 - 1992/10/16
N2 - The 2-deoxy-d-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n, basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticula. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands13, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.
AB - The 2-deoxy-d-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n, basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticula. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands13, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.
KW - 1,3-Di-o-tolylguanidine
KW - 2-Deoxy-Deoxy-d-glucose
KW - Local cerebral glucose utilization
KW - Sigma ligand
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U2 - 10.1016/0006-8993(92)91317-8
DO - 10.1016/0006-8993(92)91317-8
M3 - Article
C2 - 1450934
AN - SCOPUS:0026761853
SN - 0006-8993
VL - 593
SP - 265
EP - 273
JO - Brain Research
JF - Brain Research
IS - 2
ER -