Increase of noradrenaline release in the hypothalamus of freely moving rat by postsynaptic 5-hydroxytryptamine1A receptor activation.
1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-(3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4. The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5. Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6. Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7. The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day for 2 weeks). 8. The present results suggest that activation of postsynaptic 5-HT1A receptors increases NA release in the hypothalamus.
Suzuki
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Matsuda
T
T
Asano
S
S
Somboonthum
P
P
Takuma
K
K
Baba
A
A
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology*; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D014326:Tropanes / Q000008:administration & dosage / Q000494:pharmacology
D004146:Dioxanes; D004149:Dioxoles; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C096294:osemozotan; C042253:bemesetron; D002065:Buspirone; D009638:Norepinephrine