Ang II and Ang III modulate PTZ seizure threshold in non-stressed and stressed mice: Possible involvement of noradrenergic mechanism

Abstract

The present study evaluated the effects of Angiotensin (Ang) Ang II and Ang III on pentylenetrazol (PTZ) seizure threshold in non-stressed and stressed mice as well as the possible participation of noradrenergic (NA) mechanism in their effects. While intracerebroventricular (i.c.v.) administered Ang II and Ang III increased the PTZ threshold for myoclonic twitch (MTW), generalized clonus (GNCL) and tonic hindlimb extension (THE) in non-stressed mice, they attenuated the anticonvulsant effects of acute restraint stress. The selective AT(1) receptor antagonist losartan rather than the selective AT(2) receptor antagonist PD 123319 antagonized the effects of Ang II in both non-stressed and stressed animals. Losartan also reversed the effects of Ang III on the thresholds for MTW and GNCL in stressed mice. Concurrent administration of desipramine (NA-uptake inhibitor) and either Ang II or Ang III produced a greater effect on MTW and GNCL in non-stressed mice. However, desipramine reversed the peptide-induced attenuation on PTZ seizure threshold in stressed mice. Prazosin (alpha(1)-adrenoreceptor (AR) antagonist) blocked the effects of Ang II on PTZ seizure threshold for the three convulsive phases in both non-stressed and stressed mice. Prazosin potentiated the anti-seizure effect of Ang III against MTW, GNCL, and THE in non-stressed mice while it reversed the seizure threshold-decreasing effect of this heptapeptide on MTW and GNCL in stressed mice. Yohimbine (alpha(2)-AR antagonist) blocked only the effects exerted by Ang II on the PTZ seizure threshold in non-stressed mice. Our findings suggest that the responses of Ang II and Ang III on PTZ seizure threshold can be mediated by AT(1) receptors in non-stressed and even more in stressed mice. We also hypothesize that the NA-dependent mechanism plays a major role in the effects of Ang peptides in both non-stressed and stressed mice.