Purpose: The neurobiological relationships between epilepsy and depression are receiving increased experimental attention. A key role for limbic monoamines in depression has been established and we recently showed the importance of hippocampal dopamine and serotonin in limbic seizure control. We here evaluated the anticonvulsant effect of the noradrenergic antidepressant maprotiline and screened for associated neurochemical effects on extracellular hippocampal noradrenaline, dopamine, serotonin, GABA and glutamate.
Method: . In vivo intracerebral microdialysis was used in rats to administer maprotiline intrahippocampally and to sample the
hippocampal extracellular space. Concentration-response experiments were conducted with a wide range of maprotiline perfusion concentrations (1nM-100_M). Following maprotiline pretreatment, acute limbic seizures were induced by intrahippocampal perfusion with 10mM pilocarpine for 40 min. Seizure severity assessment was based on the observation of behavioural manifestations according to an inhome validated seizure severity scoring system.
Results: From 250nM concentration onwards maprotiline potently inhibited limbic seizures. Remarkably, at the highest concentrations (10 and 100_M) maprotiline was proconvulsant as pilocarpine-induced seizure severity was potentiated. Intrahippocampal maprotiline perfusion concentration-dependently increased extracellular hippocampal noradrenaline and dopamine levels from 100nM onwards, and serotonine and glutamate levels from 10_M onwards. GABA-ergic effects were only observed with anticonvulsant maprotiline concentrations.
Conclusion: Within a limited concentration range maprotiline mediates potent inhibitory effects on acute limbic convulsions. These anticonvulsant effects are associated with significant increases in noradrenaline, dopamine and GABA levels. Proconvulsant effects are associated with excessive noradrenaline and dopamine increases, serotonin and glutamate increases and suppression of GABA-ergic activity.
Original languageEnglish
Title of host publicationEpilepsia
Publication statusPublished - 2008
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009

Publication series

NameEpilepsia

Conference

ConferenceFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet
CountrySweden
CityStockholm
Period21/09/0925/09/09

    Research areas

  • maprotiline, epilepsy, hippocampus, noradrenalin

ID: 1751338