Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain.
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 reticulata. 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 ligands, 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.
Hohmann
A G
AG
Schrier Research Laboratory, Department of Psychology, Brown University Providence, RI 02912.
Matsumoto
R R
RR
Hemstreet
M K
MK
Patrick
S L
SL
Margulies
J E
JE
Hammer
R P
RP
Walker
J M
JM
D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D006146:Guanidines; D017480:Receptors, sigma; D003847:Deoxyglucose; D005947:Glucose; C050232:1,3-ditolylguanidine