Fear behavior and regional brain monoamines distribution after R(+)-8-OHDPAT and R(+)-UH-301 injections into the dorsal raphe nucleus in rats
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The effects of R(+)-8-Hydroxy-dipropyl-aminotetralin, (R(+)-8-OHDPAT) and R(+)-5-Fluoro-Hydroxy-dipropyloaminotetralin (R(+)-UH-301) injection into the dorsal raphe nucleus (DRN) on fear behavior in a modified version of the light-dark transitions test and regional brain monoamines (NA, DA, 5-HT) and their metabolites ( MHPG, DOPAC, 5-HIAA) in the hypothalamus (HPT), midbrain central gray matter (MID), amygdala (AMY), hippocampus (HIP) and pons (PO) were examined. An injection of R(+)-8-OHDPAT (300 ng) as well R(+)-UH-301 (300 ng) into the DRN evoked i) an increase in the number of head dipping from dark to the illuminated compartment of chamber; ii) an increase of time spent motionless in the dark compartment; iii) decrease of time of locomotion activity in the illuminated compartment. There was no effect on (1) time out from the illuminated to the dark compartment; (2) time of locomotion activity in the dark compartment; (3) time spent motionless in the illuminated compartment; 4) the number of returns from the dark to the illuminated compartment. HPLC analysis showed reduction of 5-HIAA/5-HT ratio in the HPT, HIP and PO, reduction of 5-HT in the MID, increase of NA content in the HPT and AMY, increase of MHPG/NA ratio in the HIP and PO, and increase of DA content in the HPT, AMY and HIP and increase of DOPAC content in the HIP after R(+)-8-OHDPAT injection into the DRN. But injection of R(+)-UH-301 into the DRN reduced 5-HT in the MID and increased in the AMY, reduced 5-HIAA content in the HIP and increased in the MID, reduced NA content in the HIP and increased in the HPT and decreased MHPG/NA ratio in the PO. These results indicate that both 5-HT1A receptor agonists, R(+)-8-OHDPAT and R(+)-UH-301, acting on the 5HT1A autoreceptors caused the anxiolytic effects, reduced fear behavior on the rat connected with infringement of dynamic balance between the serotonergic and catecholaminergics systems.
Publication order reference
M. Koprowska, Department of Neurophysiology, University of Lodz, 66 Rewolucji 1905 r. St., 90-222 Lodz, Poland