The tetracyclic antidepressant mianserin: evaluation of its blockade of presynaptic alpha-adrenoceptors in a self-stimulation model using clonidine.

It has been suggested that the tetracyclic antidepressant mianserin may be an antagonist at inhibitory presynaptic alpha-adrenoceptors. If mianserin exerted a selective antagonist effect it should produce effects that are essentially opposite to those of a selective agonist such as clonidine. This hypothesis was investigated in a shuttle-box self-stimulation model previously shown to be sensitive to alpha-adrenergic drugs. In this model a presynaptic alpha-adrenoceptor antagonist would be expected to enhance self-stimulation and to reverse the inhibitory effects of clonidine. Mianserin (2.5-4.0 mg/kg) did not enhance self-stimulation, but instead produced a selective inhibition of reward. Further, mianserin did not reverse the inhibitory effects of clonidine on self-stimulation. These data suggest that if mianserin is an antagonist of the presynaptic alpha-adrenoceptors it is not a selective antagonist. It is possible that the presynaptic alpha-adrenoceptor antagonism may be effects on postsynaptic alpha-adrenoceptors and/or on a presynaptic noradrenaline reuptake mechanism.