Enhancement of central dopaminergic activity in the kainate model of temporal lobe epilepsy: implication for the mechanism of epileptic psychosis.
There is an increased incidence of schizophrenia-like psychosis in temporal lobe epilepsy (TLE), and several risk factors have been implicated, including the duration of epilepsy and temporal lobe neuropathology. To investigate the biological mechanism of epileptic psychosis, we examined alterations of central dopaminergic systems in the kainate model of TLE. In adult rats, kainate was microinjected into the left amygdala to induce status epilepticus. An indirect dopamine agonist methamphetamine (MAP, 2 mg/kg, i.p.) was administered before and 1 month after the kainate treatment. MAP-induced locomotor activity was significantly enhanced in the kainate group compared with the baseline (pre-kainate) level, which was antagonized by pretreatment with haloperidol. The enhancement of locomotor activity in the kainate group was significantly correlated with the density of hippocampal CA1 neurons. Although the basal extracellular dopamine concentration was significantly lower in the striatum in the kainate group than in the control group (5.5 vs 39.2 fmol/20-min sample), the maximal concentration following MAP administration did not differ between the two groups. These results clearly demonstrate that hypersensitivity of the dopamine systems develops in the chronic phase of the kainate-induced TLE model, which may be responsible for the mechanism of epileptic psychosis.
Ando
Nobuo
N
Department of Neuropsychiatry, Faculty of Medicine, Kagawa University, Kagawa, Japan. andou-no@au6.mopera.ne.jp
Morimoto
Kiyoshi
K
Watanabe
Takemi
T
Ninomiya
Takashi
T
Suwaki
Hiroshi
H
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004563:Electrochemistry / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D011618:Psychotic Disorders / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D006220:Haloperidol; D007608:Kainic Acid; D004298:Dopamine