On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat
Section snippets
Animal preparation
Eighteen male Sprague–Dawley (Mol:SPRD) rats weighing 240–295 g at implantation were used in the experiments. Rats were kept on a 12 h light/12 h dark schedule with lights on at 06:00 h. To induce surgical anaesthesia animals were injected s.c. with 0.6–0.8 ml of a mixture of fentanyl, 0.05 mg/ml; fluanizone. 2.5 mg/ml; and midazolam l.25 mg/ml (Hypnorm Janssen–Dormicum Roche) diluted with distilled water. Temgesic (buprenorphin) was used for postoperative analgesia (0.1–0.2 ml, s.c.). Animals were
Results
There were no unusual behavioural changes during the experiments. In each rat the average 5-HT level in W was higher than in SWS and REM sleep irrespectively of the time of the day (data not shown).
Discussion
This is the first study to our knowledge to monitor brain extracellular 5-HT levels in DRN and FC in freely moving rats, with simultaneous EEG–EMG recording of sleep and waking stages. It also confirms the suitability of the microdialysis technique to the study of sleep physiology and neurochemistry in rats.
Several technical details were carefully analysed in consideration of the narrow dimension of the DRN in rats. First of all we minimized the probe size (1 mm tip), we carefully verified the
Conclusions
Extracellular 5-HT levels in DRN show a strong correlation with the behavioural states. Our data also suggest that the release of 5-HT in FC is correlated to the sleep/wake cycle in the same manner as DRN release. The data stress the importance of controlling for behavioural state when investigating neurochemical correlates of serotonergic function.
Acknowledgements
This study was supported in part by the Norwegian Research Council for Science and the Humanities.
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2018, European Journal of PharmacologyCitation Excerpt :However, the same has not occurred in the study by De Simoni et al. (1987), where there has been an increase in 5-hydroxyindolacetic acid, but not in 5-HT with administration of Trp throughout the day. The levels of cerebral 5-HT vary throughout the day, as its release occurs rhythmically (Paulus and Mintz, 2012; Versteeg et al., 2015; Weiner et al., 1992), with higher levels in the dark-cycle period, as the release of 5-HT in the dorsal raphe nucleus and the frontal cortex is correlated with the sleep–wake cycle (Portas et al., 1998). This can be explained by the variations in the serotonergic receptors mRNA expression and 5-HT uptake by its transporter, SERT (Ushijima et al., 2005).
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