Regional changes in brain 2-14C-deoxyglucose uptake induced by convulsant and non-convulsant doses of lindane.
Lindane-induced dose- and time-related changes in regional 2-14C-deoxyglucose (2-DG) uptake were examined in 59 discrete rat brain structures using the 2-DG autoradiographic technique. At different times (0.5-144 hr) after administration of a seizure-inducing single dose of lindane (60 mg/kg), 2-DG uptake was significantly increased in 18 cortical and subcortical regions mainly related to the limbic system (e.g., Ammon's horn, dentate gyrus, septal nuclei, nucleus accumbens, olfactory cortex) and extrapyramidal and sensory-motor areas (e.g., cerebellar cortex, red nucleus, medial vestibular nucleus). There was also a significant increase in superior colliculus layer II. In addition, significant decreases occurred in a group of 6 regions (e.g., auditory and motor cortices). Non-convulsing animals treated with the same dose of lindane showed a regional pattern of 2-DG uptake less modified than the convulsant group. A non-convulsant single dose of lindane (30 mg/kg) also modified significantly the 2-DG uptake (0.5-24 hr) in some brain areas. Although the various single doses of lindane tested produced different altered patterns of brain 2-DG uptake, some structures showed a similar trend in their modification (e.g., superior colliculi and accumbens, raphe and red nuclei). Repeated non-convulsant doses of lindane produced defined and long-lasting significant elevations of 2-DG uptake in some subcortical structures (e.g., dorsal cochlear nucleus, dentate gyrus). Considering the treated groups all together, 2-DG uptake increased significantly in 26 of the 59 regions examined but only decreased significantly in 9 of them during the course of lindane effects. This fact can be related to the stimulant action described for this neurotoxic agent. The observed pattern provides a descriptive approach to the functional alterations occurring in vivo during the course of lindane intoxication. These results may be linked to the proposed mechanism of lindane neurotoxicity postulating an initial action on the GABAA receptor-chloride channel sites.
Sanfeliu
C
C
Department of Pharmacology and Toxicology, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
Solà
C
C
Camón
L
L
Martínez
E
E
Rodríguez-Farré
E
E
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002250:Carbon Radioisotopes; D003837:Deoxy Sugars / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D001556:Hexachlorocyclohexane / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced; D014018:Tissue Distribution
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D003837:Deoxy Sugars; D001556:Hexachlorocyclohexane; D003847:Deoxyglucose