The role of dopamine in epilepsy

Abstract

The clinical benefits of dopamine agonists in the management of epilepsy can be traced back over a century, whilst the introduction of neuroleptics into psychiatry practice 40 years ago witnessed the emergence of fits as a side effect of dopamine receptor blockade. Epidemiologists noticed a reciprocal relationship between the supposed dopaminergic overactivity syndrome of schizophrenia and epilepsy, which came to be regarded as a dopamine underactivity condition. Early pharmacological studies of epilepsy employed nonselective drugs, that often did not permit dopamine's antiepileptic action to be clearly dissociated from that of other monoamines. Likewise, the biochemical search for genetic abnormalities in brain dopamine function, as predeterminants of spontaneous epilepsy, proved largely inconclusive. The discovery of multiple dopamine receptor families (D1 and D2), mediating opposing influences on neuronal excitability, heralded a new era of dopamine‐epilepsy research. The traditional anticonvulsant action of dopamine was attributed to D2 receptor stimulation in the forebrain, while the advent of selective D1 agonists with proconvulsant properties revealed for the first time that dopamine could also lower the seizure threshold from the midbrain. Whilst there is no immediate prospect of developing D2 agonists or D1 antagonists as clinically useful antiepileptics, there is a growing awareness that seizures might be precipitated as a consequence of treating other neurological disorders with D2 antagonists (schizophrenia) or D1 agonists (parkinsonism). © 1996 Wiley‐Liss, Inc.

The control of seizures by the basal ganglia? A review of experimental data

“…These data are in agreement with previous results showing a suppression of absence-seizures in GAERS following systemic injection of dopamimetics, whereas aggravation was observed after injection of dopamine antagonists [86]. Altogether, data observed in the genetic model of absence epilepsy are also in agreement with the antiepileptic effects of dopamimetic drugs, which have been reported in both human and in animals (for review, see [87]).…”

Alteration of dopamine D2/D3 receptor binding in patients with juvenile myoclonic epilepsy

“…Our findings are in line with this interpretation, as greater D2‐mediated striatal autoinhibition could indeed be due to an increased occupancy of D2/D3 receptors by dopamine, which could lead to a competitive displacement of [18F]FP. This explanation would support the hypothesis of a tonic high state of dopamine activity in epilepsy (Starr, 1996; Chen, 2006). The lack of behavioral stimuli and the long duration of data acquisition during PET data acquisition make it more likely that the observed alterations in D2 binding are due to changes in tonic rather than phasic dopamine release (Grace, 1991).…”

Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy

“…Previous reports have shown that the absence of D2R (Drd2 −/− mice) leads to a lower seizure threshold and increased neurotoxicity in response to treatment with both kainic acid and pilocarpine in comparison to wild-type mice (Bozzi et al, 2000;Bozzi and Borrelli, 2002). These data support the idea that D2R may act as a neuroprotective agent by reducing seizure activity and extensive hippocampal neuronal death (Starr, 1996;Bozzi et al, 2000;Bozzi and Borrelli, 2002;Brodie et al, 2016). Increased expression of Drd2 as reported here may reflect a protective response against PPS-induced neurodegeneration during early epileptogenesis.…”