α_2ヘテロ受容体を介するセロトニン遊離調節機構の脱感作 Subsensitivity of the presynapticα_2-adrenoceptors (heteroreceptors) that regulate serotonergic neuronal function

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In vivo microdialysis was used to measure the effects of long-term treatment of rats with desipramine upon the regulation by α<SUB>2</SUB>-adrenoceptors of serotonin (5-HT) release from the serotonergic neurons in the hippocampus. Extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusate using HPLC-ECD. When the α<SUB>2</SUB>-adrenoceptor agonist brimonidine was added to the perfusion solution, the K<SUP>+</SUP>-evoked 5-HT release was significantly inhibited in a concentration-dependent manner. Treatment with pertussis toxin did not alter the K<SUP>+</SUP>-evoked release of 5-HT but abolished the inhibitory effect of brimonidine. Long-term desipramine treatment significantly reduced the inhibitory effect of brimonidine upon the K<SUP>+</SUP>-evoked 5-HT release, and both the 5-HT content of the hippocampus and the basal 5-HT concentration in the dialysate were significantly increased. The present study suggests that long-term administration of desipramine causes a functional subsensitivity of the presynaptic α<SUB>2</SUB>-adrenoceptors that regulate serotonergic neuronal function in the rat hippocampus. It also supports the concept that changes in the sensitivity of α<SUB>2</SUB>-adrenoceptors that regulate neurotransmitter release play an important role in the mechanism of antidepressant drug action.

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  • 日本薬理学雑誌

    日本薬理学雑誌 106, 157-161, 1995-09-01

    公益社団法人 日本薬理学会

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