Role of the central serotonergic system in the anticonflict effect of d-AP159.
d-AP159 is a d-optical isomer, and in rats it has a high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors and potent anticonflict activity, equal to that of buspirone. The anticonflict effects of d-AP159 and buspirone were investigated in animals in which lesions of the serotonergic neurons were caused by intradorsal raphe (d-RA) injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). The anticonflict effect of buspirone, but not that of d-AP159, was attenuated in 5-HT neuron-lesioned rats. The anticonflict effect of d-AP159 injected into various brain sites was also studied. d-AP159 and buspirone microinjected into the d-RA caused significant anticonflict activity in rats. There was a significant anticonflict effect of d-AP159 injected into the amygdala centralis (ACE), but not the dorsal hippocampus (d-HC). The anticonflict effect of d-AP159 injected into the d-RA was antagonized by systemic administration of (-)propranolol but not Ro 15-1788. This effect of d-AP159 injected into the ACE was antagonized by systematic administration of Ro 15-1788 but not (-)propranolol. These results suggest that the d-RA and the ACE play important roles in the anticonflict effects of d-AP159 but that the mechanisms by which this drug acts at these sites are different.
Department of Pharmacology, Nobeoka Medicines Laboratory, Asahi Chemical Industry Co., Ltd., Miyazaki, Japan.
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Takao
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Nagatani
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Kasahara
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Hashimoto
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003220:Conflict, Psychological; D004563:Electrochemistry; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011433:Propranolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013237:Stereoisomerism; D058924:Thienopyridines
D014151:Anti-Anxiety Agents; D011725:Pyridines; D058924:Thienopyridines; C066285:N-cyclohexyl-1,2,3,4-tetrahydro(1)benzothieno(2,3-c)pyridine-3-carboxamide; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D005442:Flumazenil; D011433:Propranolol; D002065:Buspirone