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.
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M. Koprowska, Department of Neurophysiology, University of Lodz, 66 Rewolucji 1905 r. St., 90-222 Lodz, Poland