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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.