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.

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

“…However, in mice, 5HT loss is milder, while a severe DA depletion occurs, as described in detail by the Colado's group (Colado et al, 2001) and shown by other studies (Stone et al, 1987;Logan et al, 1988;Ali et al, 1991;Cadet et al, 1995;Fornai et al, 2001Fornai et al, , 2004b. Both monoamines might modulate seizures (see, for instance, Pasini et al, 1996;Starr, 1996;Heisler et al, 1998;Torta and Monaco, 2002;Giorgi et al, 2003Giorgi et al, , 2004. However, this is unlikely to occur in the present study.…”

Effect of γ-ethyl-γ-phenyl-butyrolactone (EFBL), anticonvulsant and hypnotic drug, on mouse brain catecholamine levels

“…In 1996, a glutamate-DA interaction proposed by Starr attempted to explain the individual susceptibility to epilepsy in limbic areas (24). According to this hypothesis, in the epileptic brain there is increased tonic excitation of DA neurons by glutamate (Glu) due to the peroxisomal activity on the cortex.…”

“…Another important finding is the promotion of seizures observed in patients with no previous history of epilepsy via the use of antipsychotics that act as DA-ergic D2-like antagonists. In contrast, seizure inhibition has been observed when antiparkinsonian drugs, such as pergolide and bromocriptine, which both act by stimulating D2Rs, are administered (24).…”

Association of Epilepsy and Tourette Syndrome in Children

“…The pathophysiology of epilepsy and TS remains unclear, yet abnormal cortico-basal ganglion circuit connections and dopaminergic systems are possibly involved [9]. Alternations of dopaminergic neurotransmission and corticostriatal network are substantially evident in TS.…”