Effects of 8-OH-DPAT on hippocampal NADH fluorescence in vivo in anaesthetized rats

Abstract

Systemic administration of the 5-HT1A receptor agonist 8-OH-DPAT modifies 5-HT neuronal transmission via stimulation of presynaptic and postsynaptic receptors. Compared to the effects of presynaptic receptor stimulation, there are less data on the effects of postsynaptic 5-HT1A receptors and the net effects of a stimulation of pre- and postsynaptic 5-HT1A receptors available. We measured the neuronal activity in the rat hippocampus after systemic treatment with 8-OH-DPAT in doses (30-300 microg/kg) known to reduce 5-HT release and anxiety-like behavior in rodents. Neuronal activity was assessed by laser-induced fluorescence spectroscopy determining changes in nicotinamide adenine dinucleotide (NADH) fluorescence in the ventral hippocampus of anaesthetized rats in vivo. NADH, a co-substrate for energy transfer in the respiratory chain, mirrors mitochondrial activity. Increased NADH fluorescence signals lower consumption of NADH caused by neuronal inhibition. 8-OH-DPAT in a dose of 300 microg/kg, but not 100 microg/kg and 30 microg/kg, increased NADH fluorescence by maximal +27 +/- 3.5%, suggesting a decreased neuronal activity in the ventral hippocampus. The selective 5-HT1A antagonist WAY-100635 (3 mg/kg) prevented the increased NADH fluorescence after 8-OH-DPAT, but had no own effect. The results show that systemic administration of the 5-HT1A agonist 8-OH-DPAT dose-dependently affects neuronal activity in the ventral hippocampus. The dose of 300 microg/kg seemingly activates presynaptic and postsynaptic receptors with dominating inhibitory postsynaptic effects.

Neurotransmitter and Behaviour: Serotonin and Anxiety

“…Complementary to established methods, the laser-induced fluorescence spectroscopy offers the possibility of "on line" -measurements of the metabolic state of intact tissues. After verification that in vivo laser-induced fluorescence spectroscopy detects changes in mitochondrial/metabolic activity in the CNS, we determined the mitochondrial activity in the ventral hippocampus after administration of the 5-HT1A agonist 8-OH-DPAT (Rex and Fink 2006). Systemic administration of 8-OH-DPAT induced dose-dependent changes in mitochondrial activity of hippocampal neurons.…”

Altered nicotinamide adenine dinucleotide (NADH) fluorescence in dtsz mutant hamsters reflects differences in striatal metabolism between severe and mild dystonia

“…Concentrations of nicotinamide adenine dinucleotide (NADH), a cosubstrate for energy transfer in the respiratory chain, mirror mitochondrial oxidative metabolism in vitro (Shuttleworth et al, 2003) as well as in vivo (Ince et al, 1992; Rex et al, 1999). Determination of changes in NADH fluorescence, reflecting changes in CNS metabolism with high spatial and time resolution using laser‐induced fluorescence spectroscopy in vivo, is an established method (Mottin et al, 2003; Rex and Fink, 2006a, b). Therefore, this technique was used to measure metabolic activity, indicating changes in neuronal activity.…”

Effects of 5HT1A Activation on Gating Profile Following 5HT Depletion in Rats Lacking Social Attachment Since Weanling

“…While 5,7-DHT exerts its effects presynaptically, 8-OH-DPT executes it effects pre and post-synaptically, because 5-HT1A receptors may be expressed in both places [ 25 , 26 ]. Second, 8-OH-DPT at the dose used in the present study (i.e., 100 μg/kg) is generally inadequate to activate the postsynaptic 5-HT1A receptors [ 27 ], however since the IR rats characteristically may have a supersensitive profile of the post-synaptic 5-HT1A receptor [ 11 ]. the 5,7-DHT-readjusted presynaptic function may affect the tonicity/balance between pre and post-synaptic 5-HT1A receptors, and therefore responsible for the diverse effects of 8-OH-DPT on PPI in IR-sham and IR-depletion rats.…”