Fachbereich Veterinärmedizin



    Effects of the 5-HT1A agonist 8-OH-DPAT on mitochondrial activity in the ventral hippocampus of anaesthetised rats (2005)

    Fink, F.
    Rex, A.
    46. Frühjahrstagung der Deutschen Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (DGPT)
    Mainz, 15. – 17.03.2005
    Naunyn-Schmiedeberg´s Archives of Pharmacology; 371(Suppl. 1) — S. R30
    ISSN: 0028-1298
    Institut für Pharmakologie und Toxikologie

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    14195 Berlin
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    Abstract / Zusammenfassung

    5-HT1A receptors, distributed largely throughout the CNS, have been implicated in the aetiology of numerous disease states, including depression, anxiety disorders and eating disorders. 5-HT1A receptors located in the raphé nuclei are somatodendritic and inhibit cell firing. Postsynaptic 5-HT1A receptors are present in a number of limbic structures, particularly the hippocampus.
    In the literature, there are less data on the effects of postsynaptic 5-HT1A receptor-stimulation as well as the net effects of a simultaneous stimulation of pre- and postsynaptic 5-HT1A receptors, compared to the effects of presynaptic receptor-stimulation.
    Following systemic treatment with 8-OH-DPAT in doses with known anxiolytic-like effects (30 – 300 µg/kg, i.p.) we assessed the neuronal activity in the ventral hippocampus (coordinates: ML 4.7 mm, AP -5.6 mm from bregma, depth -7.5 mm from brain surface) of male Wistar rats (Shoe: Wist, Dimed GmbH, Germany) anaesthetised with chloral hydrate (380 mg/kg, i.p.). Mitochondrial activity was measured by laser-induced fluorescence spectroscopy determining changes in nicotinamide adenine dinucleotide (NADH) fluorescence. NADH, a co-substrate for energy transfer in the respiratory chain, mirrors mitochondrial activity which is closely linked to neuronal activity. Increased NADH fluorescence indicates neuronal inhibition associated with lower NADH consumption. 8-OH-DPAT (300 µg/kg) increased NADH fluorescence by 27.0±3.5%, implying decreased neuronal activity in the ventral hippocampus. The area under the curve (AUC) during the subsequent 120 minutes post treatment was increased to 125.8±7.5 compared to the controls (AUC=105.1±6.1). 8-OH-DPAT at a dose of 100 µg/kg had no effect (AUC= 103.1±6.4), whereas the lowest dose of 30 µg/kg tended to decrease NADH fluorescence (AUC=90.6±5.5).
    The results show that systemic administration of 8-OH-DPAT dose-dependently affects neuronal activity in the ventral hippocampus. The dose of 300 µg/kg seemingly activates presynaptic and postsynaptic 5-HT1A receptors with dominating inhibitory postsynaptic effects.