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Differences in the mechanisms that increase noradrenaline efflux after administration of d-amphetamine: a dual-probe microdialysis study in rat frontal cortex and hypothalamus

Geranton, SM; Heal, DJ; Stanford, SC; (2003) Differences in the mechanisms that increase noradrenaline efflux after administration of d-amphetamine: a dual-probe microdialysis study in rat frontal cortex and hypothalamus. BRIT J PHARMACOL , 139 (8) 1441 - 1448. 10.1038/sj.bjp.0705396.

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Abstract

1 The extent to which impulse-independent release of noradrenaline and/or inhibition of its reuptake contribute to the response to d-amphetamine in vivo is unclear. Here, dual-probe microdialysis was used to investigate this question in the rat frontal cortex and hypothalamus.2 After systemic administration of d-amphetamine (10 mg kg(-1)), or its local infusion (10 muM), the increase in noradrenaline efflux in the hypothalamus was greater than in the frontal cortex.3 In contrast, during local infusion of the noradrenaline reuptake inhibitor, BTS 54 354 ( 50 mm), the noradrenaline response was similar in the frontal cortex and hypothalamus, even after systemic administration of the alpha(2)-antagonist, atipamezole, to block presynaptic inhibition of transmitter release and neuronal firing.4 In the frontal cortex, but not the hypothalamus, the noradrenaline response to 10 muM d-amphetamine was constrained by activation of alpha(2)-adrenoceptors. This suggests that, at this concentration, inhibition of reuptake of noradrenaline, following its impulse-dependent release, is evident in the frontal cortex, but that the noradrenaline response in the hypothalamus derives mostly from impulse-independent release (retrotransport).5 Atipamezole did not affect the noradrenaline response to 100 muM d-amphetamine in either brain region possibly because, at this higher concentration, retrotransport of noradrenaline masks any compensatory reduction in impulse-evoked release.6 It is concluded that inhibition of reuptake and retrotransport make different contributions to the noradrenaline response to d-amphetamine in the frontal cortex and hypothalamus and that retrotransport increases with the concentration of d-amphetamine.

Type: Article
Title: Differences in the mechanisms that increase noradrenaline efflux after administration of d-amphetamine: a dual-probe microdialysis study in rat frontal cortex and hypothalamus
DOI: 10.1038/sj.bjp.0705396
Keywords: alpha(2)-adrenoceptor, d-amphetamine, frontal cortex, hypothalamus, microdialysis, noradrenaline, LOCUS COERULEUS, EXTRACELLULAR NOREPINEPHRINE, SIBUTRAMINE, NEURONS, ALPHA(2)-ADRENOCEPTORS, ADRENOCEPTORS, MODULATION, COCAINE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/120044
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