Effects of acute and chronic electroconvulsive shock on noradrenaline release in the rat hippocampus and frontal cortex

Abstract

Changes in the extracellular content of endogenous noradrenaline (NA) in frontal cortex and hippocampus were determined by in vivo microdialysis following acute and chronic electroconvulsive shock (ECS) in rats anaesthetized with chloral hydrate. Basal release of NA in the frontal cortex (4.9 ± 0.3 pg/sample) did not differ significantly from that in the hippocampus (4.6 ± 0.2 pg/sample). A single ECS resulted in an increase of NA release in the hippocampus (21.1 ± 1.3 pg/sample) and in the frontal cortex (11.6 ± 1.2 pg/sample). In both brain regions extracellular NA had returned to basal values within 30 min. Animals were treated chronically with ECS (once per day for seven days). Twenty‐four h later (day 8), basal release of NA into dialysis samples from the frontal cortex was significantly increased (50%) as compared to chronic sham controls. Basal release in the hippocampus was not significantly different from the sham controls. In the chronic ECS animals the increase in NA released in both brain areas following an ECS on day 8 did not differ from either the chronic sham controls or from animals given acute ECS. Animals were challenged 24 h after eight ECS or sham control treatments (once per day) with the α2‐adrenoceptor antagonist, idazoxan (10 mg kg−1, s.c). Idazoxan increased NA release in the hippocampus in both groups. There was no difference in the magnitude of the response in ECS‐ and in sham‐treated rats. In the frontal cortex, idazoxan increased the extracellular NA content in the chronic sham controls, but the response to idazoxan was significantly attenuated in the chronic ECS animals. Chronic but not acute ECS was found to elicit a sustained (> 24 h) increase in the release of NA in the frontal cortex, but not in the hippocampus. The idazoxan data suggest that the increase may be due to a downregulation of presynaptic α2‐adrenoceptors in the frontal cortex. The difference in response of these two brain regions to chronic ECS is discussed in terms of differences in the regulation of extracellular NA content by uptake and autoreceptor activation.

Electroconvulsive shocks decrease α2-adrenoceptor binding in the Flinders rat model of depression

“…These data suggest that a sustained release of noradrenaline over the course of ECS in the frontal cortex may have induced a compensatory down-regulation of the presynaptic α 2 -adrenoceptors in the frontal cortex but not in hippocampus, explaining why idazoxan did not have any effect on the α 2 -adrenoceptors in frontal cortex of the ECS treated rats (Thomas et al, 1992). Our data are consistent with the observations of Subhash et al (2003) and Thomas et al (1992), finding no significant differences in the hippocampal region of the ECS treated FSL and FRL rats compared to the sham treated rats, but demonstrating down-regulation in cortical regions in the FSL rats and in cortical and amygdaloid regions in the FRL rats. Moreover, the lack of alteration in receptor binding in the hippocampal region is in line with the unresponsiveness of hippocampal pydamidal neurons to norepinephrine found following ECS (de Montigny, 1984).…”

“…However, it must be noted that post-mortem changes in binding do not always correlate with the in vivo functional response of receptors and increased sensitivity of amygdaloid neurons to monoaminergic transmitters has been found following antidepressant treatment (Wang and Aghajanian, 1980). A decreased density in α 2 -adrenoceptors was found by Subhash et al (2003) in cortical areas, but not in hippocampal areas, in the rat brain after chronic treatment with tricyclic antidepressants suggesting region-specific down-regulation and Thomas et al (1992) found a release of noradrenaline 24 h after the last chronic ECS treatment session in rat frontal cortex, but not in hippocampus, compared to sham treated controls. Furthermore, when Thomas et al (1992) challenged these rats with the α 2 -adrenoceptor antagonist idazoxan, increased release of noradrenaline was found in the sham treated rats in both brain regions, but in the chronically ECS treated rats, the release was only observed in the hippocampus.…”

“…A decreased density in α 2 -adrenoceptors was found by Subhash et al (2003) in cortical areas, but not in hippocampal areas, in the rat brain after chronic treatment with tricyclic antidepressants suggesting region-specific down-regulation and Thomas et al (1992) found a release of noradrenaline 24 h after the last chronic ECS treatment session in rat frontal cortex, but not in hippocampus, compared to sham treated controls. Furthermore, when Thomas et al (1992) challenged these rats with the α 2 -adrenoceptor antagonist idazoxan, increased release of noradrenaline was found in the sham treated rats in both brain regions, but in the chronically ECS treated rats, the release was only observed in the hippocampus. These data suggest that a sustained release of noradrenaline over the course of ECS in the frontal cortex may have induced a compensatory down-regulation of the presynaptic α 2 -adrenoceptors in the frontal cortex but not in hippocampus, explaining why idazoxan did not have any effect on the α 2 -adrenoceptors in frontal cortex of the ECS treated rats (Thomas et al, 1992).…”

“…Furthermore, when Thomas et al (1992) challenged these rats with the α 2 -adrenoceptor antagonist idazoxan, increased release of noradrenaline was found in the sham treated rats in both brain regions, but in the chronically ECS treated rats, the release was only observed in the hippocampus. These data suggest that a sustained release of noradrenaline over the course of ECS in the frontal cortex may have induced a compensatory down-regulation of the presynaptic α 2 -adrenoceptors in the frontal cortex but not in hippocampus, explaining why idazoxan did not have any effect on the α 2 -adrenoceptors in frontal cortex of the ECS treated rats (Thomas et al, 1992). Our data are consistent with the observations of Subhash et al (2003) and Thomas et al (1992), finding no significant differences in the hippocampal region of the ECS treated FSL and FRL rats compared to the sham treated rats, but demonstrating down-regulation in cortical regions in the FSL rats and in cortical and amygdaloid regions in the FRL rats.…”

“…ECS also potentiates the release of noradrenaline; rats chronically treated with ECS have significantly increased release of noradrenaline from the frontal cortex as compared to chronic sham controls, which probably mediates a compensatory down-regulation of the presynaptic α 2 -adrenoceptors (Thomas et al, 1992).…”