Effects of 8-OH-DPAT on hippocampal NADH fluorescence in vivo in anaesthetized rats.
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.
Rex
Andre
A
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany. andrerex@zedat.fu-berlin.de
Fink
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007834:Lasers; D008297:Male; D009243:NAD / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D010775:Photic Stimulation; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D009243:NAD; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin