Ž . Brain Research 831 1999 155–164 Research report 8-OH-DPAT-sensitive neurons in the nucleus raphe magnus modulate thermoregulatory output in rats Nancy J. Berner b, ) , Dennis A. Grahn a , H. Craig Heller a a Department of Biological Sciences, Stanford UniÕersity, Stanford, CA 94305-5020, USA b Department of Biology, the UniÕersity of the South, Sewanee, TN 37383-1000, USA Accepted 23 March 1999 Abstract Ž . The nucleus raphe magnus NRM is purported to be a relay through which peripheral thermoafferent information is transmitted to Ž . thermointegrative centers located in the preopticranterior hypothalamus POAH . Therefore, suppression of neural activity in the NRM should reduce thermoregulatory responses to peripheral thermal challenges, but not affect responses elicited by manipulation of POAH temperature. At low ambient temperatures lidocaine injections into the NRM of nonanesthetized rats resulted in decreases in POAH temperature, oxygen consumption, and electromyographic activity. At a warm ambient temperature, lidocaine injections into the NRM decreased the elevations in oxygen consumption and electromyographic activity elicited by cooling the POAH. The effects of lidocaine Ž . injections were duplicated by injection of a 5-HT agonist 8-hydroxy-dipropylaminotetralin 8-OH-DPAT into the NRM. The effect of 1A 8-OH-DPAT was eliminated by pre-treatment with a selective autoreceptor antagonist. These results suggest that NRM 5-HT neurons are modulating the relationship between output of thermointegrative centers and thermoregulatory effector responses rather than processing thermoafferent information. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Lidocaine; 8-OH-DPAT; Serotonin; Nucleus raphe magnus; O consumption; EMG 2 1. Introduction Ž . There is evidence that the nucleus raphe magnus NRM is involved in thermoregulatory processing. Single unit Ž recordings in anesthetized animals without concomitant Ž . recording of cortical electroencephalographic EEG activ- . ity indicated a correlation between changes in the firing rates of cells in the NRM and the application of a periph- wx eral thermal stimulus 8 , and electrical stimulation of the NRM of cold-stressed guinea pigs inhibited cold-induced w x thermogenesis 5,12 . The inhibition was characterized by Ž . a decrease in oxygen O uptake, decreased electromyo- 2 Ž . graphic EMG activity, and a decline in body temperature Ž . T . Additionally, electrolytic lesions of the NRM in b guinea pigs resulted in a decrease in T responses to b prolonged cold or warm exposure and caused a narrowing w x of their thermoneutral zones 27 . In consideration of all of these findings, it was proposed that the NRM is a ther- ) Corresponding author. Fax: q1-931-598-1145; E-mail: nberner@sewanee.edu moafferent relay that transmits peripheral warm informa- tion to a thermointegrative center in the hypothalamus w x 6,25 . Other work, however, casts doubt on this interpretation. In unanesthetized animals, a substantial portion of the NRM neurons alter their firing rates in concert with changes w x in arousal state 16 . These arousal state selective cells Ž . have high firing rates during wakefulness W which de- crease as they enter non-rapid eye movement sleep Ž . NREMS and decrease further as they enter rapid eye Ž . movement sleep REMS . Once it was appreciated that changes in cortical EEG activity also occurred in lightly urethane-anesthetized animals, it was recognized that in anesthetized preparations the activity of most NRM cells was highly correlated with cortical EEG pattern much as it w x was in unanesthetized animals 10 . Moreover, peripheral temperature stimuli were very effective in inducing changes in cortical EEG activity in the anesthetized preparations. By manipulating skin temperature, it was possible to make NRM neurons appear to be warm- or cold-sensitive even though they were clearly temperature-insensitive as long as the EEG pattern remained constant. The conclusion was 0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01426-2