Abstract
In vivo microdialysis was used to measure the effects of long-term treatment of rats with desipramine upon the regulation by α2-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 α2-adrenoceptor agonist brimonidine was added to the perfusion solution, the K+-evoked 5-HT release was significantly inhibited in a concentration-dependent manner. Treatment with pertussis toxin did not alter the K+-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+-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 α2-adrenoceptors that regulate serotonergic neuronal function in the rat hippocampus. It also supports the concept that changes in the sensitivity of α2-adrenoceptors that regulate neurotransmitter release play an important role in the mechanism of antidepressant drug action.
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