Enhancement of Central Dopaminergic Activity in the Kainate Model of Temporal Lobe Epilepsy: Implication for the Mechanism of Epileptic Psychosis

Abstract

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.

Pilocarpine-induced temporal lobe epilepsy in the rat is associated with increased dopamine neuron activity

“…In fact we demonstrate a striking potentiation of stimulant-induced locomotor hyperactivity in pilocarpine-treated rats in accordance with previous studies made in both pilocarpine models and other models of experimental epilepsy (Ando et al, 2004; Jones et al, 2010; Ma and Leung, 2004; Muller et al, 2009; Szyndler et al, 2005). The fact that the use of a cholinergic drug reproduced aspects of TLE seen with other models suggests that it is the epileptogenic properties of the drug, rather than its cholinergic properties, that were significant in this model.…”

“…Thus, hyperactivity within the hippocampus leads to hyper-responsivity of the dopamine system, with dopamine hyper-responsivity proposed to underlie the psychotic symptoms of schizophrenia (Laruelle and Abi-Dargham, 1999). Indeed, as in this rodent model (Lodge and Grace, 2007), rats with pilocarpine-induced TLE also exhibit a substantially greater behavioral response to amphetamine (Ando et al, 2004). …”

Resting state functional network disruptions in a kainic acid model of temporal lobe epilepsy

“…The NAC has been suggested as an interface between the limbic and motor systems, which converts motivation into action (Mogenson et al, 1993). The increased limbic and prefrontal connectivity to the NAC may facilitate an increase in dopaminergic function in the NAC following kainate-induced SE (Ando et al, 2004). Similar hyperdopaminergic functions may follow kindled seizures in the amygdala and hippocampus (Adamec, 1991, Leung et al, 2000).…”

Secondary psychoses: an update

“…The striking prominence of positive symptoms in temporal lobe epilepsy has led to the question whether there might be a resemblance between temporal lobe epilepsy and the neurochemical models of schizophrenia. Ando et al examined alterations of central dopaminergic systems in the kainate model of temporal lobe epilepsy using methamphetamine‐induced locomotor activity as an index of dopaminergic sensitivity in adult rats. They found evidence of dopaminergic hypersensitivity, which can clearly explain the mechanisms underlying epileptic psychosis and can also indicate similar alterations in idiopathic psychoses.…”