BACKGROUND: The main target site of action for the sedative clonidine (CLO), an α2 adrenoceptor agonist, has been considered to be the locus coeruleus (LC). However, previous reports suggest other sites of action of CLO than the LC. Our previous studies suggested that the neuronal activities in the perifornical area (Pef) could influence the sedative or the anesthetic level induced by anesthetics. Therefore, we examined whether microinjection of CLO into the Pef might induce sedation in rats. MATERIALS AND METHODS: Fifty-five Wistar rats were used. The cortical norepinephrine (NE) and acetylcholine (ACh) effluxes were detected using microdialysis and measured by high-performance liquid chromatography in samples collected every 20 minutes. First, we injected CLO (100, 300, and 1000 μg/kg cumulative doses) intraperitoneally (IP) and observed the changes in NE or ACh efflux. Second, we injected CLO (4.8 μg in 0.2 μL) or saline (0.2 μL) into the LC or the Pef and observed the changes in NE or ACh efflux for 2 hours. Finally, a sedative/anesthetic score was obtained after IP, LC or Pef microinjection of CLO. RESULTS: IP injection of CLO induced sedation and resulted in a dose-dependent attenuation of the cortical effluxes of both NE and ACh (P<0.001). Microinjection of CLO either into the LC or the Pef induced sedation and significantly decreased the cortical NE efflux (P<0.001). Cortical ACh efflux was significantly reduced by microinjection of CLO into the Pef but not by microinjection into the LC (P<0.05). CONCLUSION: The Pef and the LC are responsible for the sedative action of CLO in rats.
BACKGROUND: The main target site of action for the sedative clonidine (CLO), an α2 adrenoceptor agonist, has been considered to be the locus coeruleus (LC). However, previous reports suggest other sites of action of CLO than the LC. Our previous studies suggested that the neuronal activities in the perifornical area (Pef) could influence the sedative or the anesthetic level induced by anesthetics. Therefore, we examined whether microinjection of CLO into the Pef might induce sedation in rats. MATERIALS AND METHODS: Fifty-five Wistar rats were used. The cortical norepinephrine (NE) and acetylcholine (ACh) effluxes were detected using microdialysis and measured by high-performance liquid chromatography in samples collected every 20 minutes. First, we injected CLO (100, 300, and 1000 μg/kg cumulative doses) intraperitoneally (IP) and observed the changes in NE or ACh efflux. Second, we injected CLO (4.8 μg in 0.2 μL) or saline (0.2 μL) into the LC or the Pef and observed the changes in NE or ACh efflux for 2 hours. Finally, a sedative/anesthetic score was obtained after IP, LC or Pef microinjection of CLO. RESULTS: IP injection of CLO induced sedation and resulted in a dose-dependent attenuation of the cortical effluxes of both NE and ACh (P<0.001). Microinjection of CLO either into the LC or the Pef induced sedation and significantly decreased the cortical NE efflux (P<0.001). Cortical ACh efflux was significantly reduced by microinjection of CLO into the Pef but not by microinjection into the LC (P<0.05). CONCLUSION: The Pef and the LC are responsible for the sedative action of CLO in rats.
Authors: Stephanie L Grella; Jonathan M Neil; Hilary T Edison; Vanessa D Strong; Irina V Odintsova; Susan G Walling; Gerard M Martin; Diano F Marrone; Carolyn W Harley Journal: J Neurosci Date: 2018-11-26 Impact factor: 6.167
Authors: Lukas Mees; Jonathan Fidler; Matthias Kreuzer; Jieming Fu; Machelle T Pardue; Paul S García Journal: PLoS One Date: 2018-10-29 Impact factor: 3.240