Studies on
dynorphin involvement in
epilepsy are summarised in this review. Electrophysiological, biochemical and pharmacological data support the hypothesis that
dynorphin is implicated in specific types of
seizures. There is clear evidence that this is true for complex partial (limbic)
seizures, i.e. those characteristic of
temporal lobe epilepsy, because; (1)
dynorphin is highly expressed in various parts of the limbic system, and particularly in the granule cells of the hippocampus; (2)
dynorphin appears to be released in the hippocampus (and in other brain areas) during
complex partial seizures; (3) released
dynorphin inhibits excitatory neurotransmission at multiple synapses in the hippocampus via activation of
kappa opioid receptors; (4)
kappa opioid receptor agonists are highly effective against limbic
seizures. Data on generalised
tonic-clonic seizures are less straightforward.
Dynorphin release appears to occur after ECS
seizures and kappa agonists exert a clear
anticonvulsant effect in this model. However, more uncertain biochemical data and lack of efficacy of kappa agonists in other generalised tonic-clonic seizure models argue that the involvement of
dynorphin in this seizure type may not be paramount. Finally, an involvement of
dynorphin in generalised absence
seizures appears unlikely on the basis of available data. This may not be surprising, given the presumed origin of absence
seizures in alterations of the thalamo-cortical circuit and the low representation of
dynorphin in the thalamus. In conclusion, it may be suggested that
dynorphin plays a role as an endogenous
anticonvulsant in
complex partial seizures and in some cases of
tonic-clonic seizures, but most likely not in generalised absence. This pattern of effects may coincide with the antiseizure spectrum of selective kappa agonists.