Down-regulation of dopamine D1 and D2 receptors in the basal ganglia of PTZ kindling model of epilepsy: effects of angiotensin IV

The present study examined the effect of pentylenetetrazol (PTZ) induced kindling as well as the action of the hexapeptide angiotensin IV (ANG IV) on the dopamine (DA) D1 and D2 receptor binding in the basal ganglia of the mouse brain. By using quantitative receptor autoradiography, it was found that PTZ kindling led to a decrease in DA D2 receptor density (about 20%) in all regions of the neostriatum (NS) as well as in the olfactory tubercle (OT), the nucleus accumbens (NA) and the globus pallidus, which persisted 24 h and 7 days after the kindling procedure. PTZ induced kindling also elicited a decrease in DA D1 receptor binding sites (about 10%), which however was, restricted to the rostral NS (rNA) and NA. ANG IV (0.2 mg/kg), injected prior to PTZ, not only prevented the development of the kindling process but it also reversed the kindling-induced down-regulation of both DA receptors to the control levels. Furthermore ANG IV induced an area-specific increase of DA D1 receptor density above control levels in the dorsal part of rNS. These findings suggest that DA D2 receptors could mainly contribute to epileptogenesis in the PTZ kindling model, whereas the role of DA D1 receptors is limited to particular regions in the basal ganglia. The anticonvulsant effect of ANG IV pretreatment might be influenced by a DA-related mechanism and particularly by preventing D2 receptor down-regulation as well as by an adaptive area-specific increase in DA D1 receptors.