Changes in pre- and postsynaptic components of noradrenergic transmission in hippocampal kindling in rats

Abstract

We investigated whether modifications in noradrenergic neurotransmission occurred during the development of hippocampal kindling in rats. We measured the release of [ 3H]norepinephrine (NE) induced by field-electrical stimulation, NE-stimulation of inositol phosphates ([ 3H]IP) accumulation in the presence of LiCl and isoproterenol-induced accumulation of cAMP in hippocampal slices taken from rats electrically kindled at stages 2 and 5 in the dorsal hippocampus. One week after the last of at least 3 consecutive stage 5 seizures or 48 h after the last stage 2 stimulation, 2 min electrical stimulation of stratum pyramidale CA1–CA3 or dentate gyrus (DG) slices from kindled and contralateral hippocampi induced frequency-dependent NE release (respectively 2, 4 and 8 times spontaneous release measured at 2, 5 and 10 Hz) which did not significantly differ from that observed in shams (implanted with electrodes but not stimulated). Basal release of NE from kindled and sham-treated rats did not differe either. Isoproterenol induced a dose-dependent increase above basal cAMP concentration ranging from 40% at 0.01 μM to 180% at 10 μM ( P < 0.01, Dunnett's test) which did not differ between stages 2 and 5 and sham-hippocampi. NE (1–1000 μM) induced a dose-dependent, prazosin-sensitive increase in [ 3H]IP accumulation in the hippocampal slices. A significantly higher increase was found at stages 2 ( P < 0.05, Tukey's test) and 5 ( P < 0.05 and P < 0.01, Tukey's test) compared to shams at all doses studied. No differences were observed in the basal cAMP or [ 3H]IP concentrations in kindled versus sham animals. No differences were observed in [ 3H]IP accumulation induced by carbachol (10, 100, 1000 μM) in stage 5-kindled rats and shams. These changes have various possible implications for kindling-induced plasticity.