Clonazepam increases in vivo striatal extracellular glucose in diabetic rats after glucose overload.
Hyperglycemia modulates brain function, including neuronal excitability, neurotransmitter release and behavioral changes. There may be connections between the GABAergic system, glucose sensing neurons and glucose in the neuronal environment that shed light on the mechanism by which GABA(A) agents influence depressive behavior in diabetic rats submitted to the forced swimming test. We aimed to investigate whether clonazepam (CNZ), a GABA(A) receptor positive modulator, modifies in vivo striatal extracellular glucose levels in diabetic rats under fasting condition or after oral glucose overload. Streptozotocin diabetic and nondiabetic rats were submitted to in vivo striatal microdialysis. Perfusate samples were collected at baseline, during fasting and following administration of CNZ (0.25 mg/kg) and oral glucose overload. Blood glucose and striatal extracellular glucose were measured simultaneously at several time points. Fasting striatal glucose levels were higher in diabetic than in nondiabetic rats and the differences between these animals were maintained after glucose overload. The increases in extracellular striatal glucose after glucose overload were around 40% and blood to brain transference was decreased in diabetics. CNZ treatment paradoxically increased striatal glucose after glucose overload in diabetic rats, which may mark the dysfunction in brain glucose homeostasis.
Gomez
Rosane
R
Pharmacology Division, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, R. Sarmento Leite 245, 90050-170 Porto Alegre, Brazil. rgomez@terra.com.br
Barros
Helena M T
HM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002998:Clonazepam / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism*; D018757:GABA Modulators / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D018757:GABA Modulators; D002998:Clonazepam; D005947:Glucose