title: Effects of general anaesthetics on 5-HT neuronal activity in the dorsal raphe nucleus.
abstract: The ascending 5-HT system has been and continues to be the subject of much research. The majority of in vivo electrophysiological and neurochemical studies of 5-HT function in rodents have been conducted in animals under anaesthesia - usually chloral hydrate or urethane. However, the effects of anaesthetics, on 5-HT function have not been systematically investigated. Here we used in vitro electrophysiology in dorsal raphe slices, to determine the effects of anaesthetically relevant concentrations of chloral hydrate (100 μM and 1 mM), urethane (10 and 30 mM), pentobarbitone (10 and 100 μM) and ketamine (10, 100 and 300 μM) on regulators of 5-HT firing activity. We examined i) basal firing (driven by α(1) adrenoceptors), ii) the excitatory response to N-methyl-d-aspartate (NMDA), iii) the 5-HT(1A) autoreceptor-mediated inhibitory response to 5-HT and iv) the GABA(A) receptor-mediated inhibitory response to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridinyl-3-ol (THIP, gaboxadol). Pentobarbitone selectively enhanced the response to THIP. Ketamine decreased basal firing, attenuated the response to NMDA, and enhanced responses to both 5-HT and THIP. Chloral hydrate had marginal effects on basal firing, slightly attenuated the NMDA response, and enhanced both the 5-HT and THIP responses. Urethane increased basal firing, decreased the NMDA response, increased the response to THIP, but had no effect on the 5-HT response. Our data indicate that all anaesthetics tested significantly affect the regulators of 5-HT neuronal function. These findings will aid in the interpretation of previous reports of in vivo studies of the 5-HT system and will allow researchers to make a rational selection of anaesthetic for future studies.
authors.affiliation: Psychobiology Research Group, Institute of Neuroscience, Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: McCardle
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gartside
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D002697:Chloral Hydrate / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D059326:Serotonergic Neurons / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D014520:Urethane / Q000494:pharmacology*
chemical_list: D018681:Anesthetics, General; D006993:Hypnotics and Sedatives; D007555:Isoxazoles; D012701:Serotonin; D014520:Urethane; D002697:Chloral Hydrate; D016202:N-Methylaspartate; D007649:Ketamine; D010424:Pentobarbital; C015542:gaboxadol