Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics.

Kitayama Tomoya

Song Liqiu

Morita Katsuya

Dohi Toshihiro

Brain Research

Alterations of norepinephrine transporter (NET) function by chroninc inhibition of NET in relation to sensitization to seizures induce by cocaine and local anesthetics were studied. [3H]norepinephrine up take into hippocampus region but not cortex, striatum or amygdalae isolated from mice treated daily for 5 days with desipramine, an inhibitor of NET was significantly decreased. Daily treatment of cocaine increased [3H]norepinephrine uptake into hippocampus. The decrease in norepinephrine uptake induced by chronic desipramine treatment was reversed by co-administration of lidocaine, bupivacaine or tricaine with desipramine. Daily administration of desipramine increased the incidence of appearance of lidocaine-induced convulsions and decreased that of cocaine-induced convulsions. The changes in the convulsive sensitivity to lidocaine and cocaine induced by repeated administration of desipramine was reversed by co-administration of lidocaine with desipramine. These results suggest that down-regulation of hippocampal NET induced by chronic administration of desipramine may be relevant to desipramine-induced sensitization of lidocaine convulsions. Inhibition of Na+ channels by local anesthetics may regulate desipramine-induced down-regulation of NET function. While repeated administration of cocaine caused up-regulation of hipoccampal NET function. Cocaine kindling developed by repeated administration of cocaine may be due to the different mechanisms from those for desipramine-induced sensitization of lidocaine seizures.

Medical sciences [ 490 ]

eng

Elsevier

Copyright (c) 2006 Elsevier Ltd.

[ISSN] 0006-8993

[DOI] 10.1016/j.brainres.2006.04.033

[NCID] AA0057324X

[PMID] 16725121

[DOI] http://dx.doi.org/10.1016/j.brainres.2006.04.033 isVersionOf