3H-Noradrenaline and 3H-5-hydroxytryptamine release from rat brain slices and its presynaptic alpha-adrenergic modulation after long-term desipramine pretreatment.

The electrically-evoked release of 3H-noradrenaline from superfused cortex and hippocampus slices was strongly enhanced (by about 50%) after long-term (4 weeks) pretreatment with desipramine (10 mg/kg, twice daily). The release-enhancing effect of the alpha-receptor antagonist phentolamine was significantly reduced but the inhibitory effects of exogenous noradrenaline and clonidine on 3H-noradrenaline release were virtually unchanged after chronic desipramine treatment. The K+ -induced release of 3H-noradrenaline from superfused synaptosomes obtained from rats pretreated with desipramine was about 25% higher than that from synaptosomes of control animals. However, noradrenaline inhibited the K+ -induced synaptosomal 3H-noradrenaline release to the same extent (viz. by about 55%) in both cases. The release of 3H-5-hydroxytryptamine induced by 26 mM K+ from cortex and hippocampus slices was not affected by chronic pretreatment with desipramine. In addition, no change was observed in the inhibitory effect of noradrenaline o 3H-5-hydroxytryptamine release. It is concluded that long-term pretreatment with desipramine leads to selective changes in the basic mechanism(s) of noradrenaline release rather than to changes in the sensitivity of presynaptic alpha-adrenoceptors.