Aims: 

The endocannabinoid system plays a central role in retrograde synaptic communication, and controls both glutamatergic and GABAergic transmission via type 1 cannabinoid receptors (CB1).

Methods: 

Distribution and synaptic localization of CB1 cannabinoid receptor was examined in different phases of pilocarpine-induced epilepsy in hippocampi of mice by immunocytochemistry. Changes were quantified after 2 h (acute phase) and 2 month (chronic phase) survival times.

Results: 

In the acute phase massive down-regulation of CB1 receptors was observed in all fields of the hippocampus. In the chronic phase of pilocarpine-induced epilepsy in mice with sclerosis, CB1 receptor-positive interneuron somata were preserved both in the dentate gyrus and in the CA1 area, and the density of CB1 immunostained fibers increased considerably in the dentate molecular layer. This suggests that, the CB1 receptor-expressing GABAergic axons sprout, and/or there is an increase of CB1 receptor levels on these fibers. The changes of CB1 immunostaining in association with the GABAergic inhibitory system appears to correlate with the severity of pyramidal cell loss in the CA1 subfield.

Conclusion: 

These results confirm the involvement of the endocannabinoid system associated with GABAergic transmission in the chronic phase of the pilocarpine model in mice. Pharmacotherapy aimed at the modulation of endocannabinoid-signaling should take into account the opposite change in CB1 receptor expression observed in the acute and chronic phase.

Support: 

NKTH-OTKA CNK 77793