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Increase of noradrenaline release in the hypothalamus of freely moving rat by postsynaptic 5‐hydroxytryptamine 1A receptor activation
Author(s) -
Suzuki M.,
Matsuda T.,
Asano S.,
Somboonthum P.,
Takuma K.,
Baba A.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14990.x
Subject(s) - medicine , hypothalamus , endocrinology , agonist , microdialysis , chemistry , 5 ht1a receptor , receptor antagonist , receptor , antagonist , 5 ht receptor , serotonin , biology , dopamine
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‐HT 1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5‐HT 1A receptor agonist, 5‐{3‐[[(2S)‐1,4‐benzodioxan‐2‐ylmethyl]amino]propoxy}‐1,3‐benzodioxole HC1 (MKC‐242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2 Subcutaneous injection of MKC‐242 (0.5mg kg _1 ) increased extracellular levels of NA and its metabolite, 3‐methoxy‐4‐hydroxyphenylglycol, in the hypothalamus and hippocampus. 3 The 5‐HT 1a 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‐HT 1A receptor antagonist. 5 Local administration of 8‐OH‐DPAT (10–100 μ m ), citalopram (1 μ m ), a 5‐HT reuptake inhibitor, and MDL72222 (10 μ m ), a 5‐HT 3 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‐HT 1A receptors increases NA release in the hypothalamus.