The effect of the potential antipsychotic ORG 5222 on local cerebral glucose utilization in freely moving rats.
The effects of administration of different doses of the potential antipsychotic Org 5222 (0.01 and 0.1 mg/kg i.v.) upon local cerebral glucose utilization (LCGU) in 102 anatomically discrete brain regions of freely moving male Wistar rats were studied with the quantitative autoradiographic [14C]2-deoxyglucose technique. Glucose utilization was significantly changed after treatment with 0.01 and 0.1 mg/kg i.v. Org 5222 in two and four brain areas, respectively. Treatment with 0.01 mg/kg Org 5222 significantly reduced LCGU in the basal thalamus (the ventral posterior medial (VPM) and lateral (VPL) nuclei). After administration of 0.1 mg/kg Org 5222, significant reductions were seen in the basal thalamus (VPL and VPM) and the medio dorsal thalamic nuclei. A highly significant elevation in LCGU was observed in the lateral nucleus of the habenula. The results show that Org 5222 selectively reduced LCGU in thalamic structures and had no or minimal effect on limbic, cortical and nigrostriatal structures, suggesting that Org 5222 may have antipsychotic potential, without inducing cognitive and extrapyramidal side-effects.
Department of CNS Pharmacology, Organon International B.V., Oss, The Netherlands.
P
P
Room
A J
AJ
Tielemans
T
T
De Boer
A M
AM
Van Delft
J A
JA
Tonnaer
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000378:metabolism; D003986:Dibenzocycloheptenes; D003990:Dibenzoxepins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D002250:Carbon Radioisotopes; D003986:Dibenzocycloheptenes; D003990:Dibenzoxepins; D006576:Heterocyclic Compounds, 4 or More Rings; D003847:Deoxyglucose; D005947:Glucose; C522667:asenapine