A Microdialysis Study of the Regulation of Endogenous Noradrenaline Release in the Rat Hippocampus

Abstract

In vivo microdialysis was used to investigate the regulation of noradrenaline release in rat hippocampus. Idazoxan, an alpha 2-adrenoreceptor antagonist (1-10 mg/kg), increased noradrenaline release in a dose-dependent manner. Inhibition of noradrenaline uptake by desipramine (0.05-20 microM; via the probe) also increased the extracellular content of the transmitter. In the presence of this increased noradrenaline content (desipramine via the probe), the effect of a low dose of idazoxan (1 mg/kg) was potentiated. Local perfusion of idazoxan (1-500 microM) in the hippocampus also increased noradrenaline release but not to the same extent as following systemic administration. In the presence of desipramine, unlike the systemic injection of idazoxan, local perfusion did not potentiate noradrenaline release. The data are consistent with the regulation of extracellular noradrenaline content in the hippocampus by neuronal uptake and to a lesser extent by presynaptic autoreceptors.

Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced by Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test

“…Our data confirm previous results in the FST (Cervo et al 1990;Kitada et al 1983), and contrast with microdialysis data suggesting that systemic idazoxan (1 mg/kg) boosts the desipramine-induced increase of NA-release (Thomas and Holman 1991). In order to study ␣ 2 -heteroreceptor-mediated inhibiting interactions on the 5-HT-system, we examined the changes induced by idazoxan on the behavioral effects produced by dual 5-HT/NA reuptake inhibition.…”

Role of Norepinephrine in Modulating Inhibitory Avoidance Memory Storage: Critical Involvement of the Basolateral Amygdala

“…In addition, they fit with previous reports suggesting that the effects of peripheral administration of 2-adrenergic compounds on learning and memory performance are mediated through a direct action on central NE release [136][137][138][139] and with previous results implicating amygdala 2-adrenoceptors in footshock-based learning [140,141]. Moreover, they clearly indicate that, in addition to involvement of 1-and -adrenoceptors, 2-adrenoceptors in the BLA are involved in mediating the effects of training-induced or experimentally administered NE on memory storage [128,131].…”

Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder

“…The selective NE transporter inhibitors nisoxetine (Wong et al 1975) and reboxetine , as well as ␣ 2 -adrenergic antagonists that enhance release of NE (Dennis et al 1987;Thomas and Holman 1991), increase burst firing of ventral tegmental DA neurons which would result in increased DA release in their terminal fields (Linnèr et al 2001;Shi et al 2000;Grenhoff and Svensson 1993).…”