Rat brain ?2-pre- and postsynaptic receptors are different or differently modulated?

Abstract

In order to get better characterization of α2-pre- and postsynaptic noradrenergic receptors in the rat brain, we investigated the α2-receptor changes which take place during a 12-day treatment with the α2-antagonists yohimbine (4 mg/kg) and mianserin (10 mg/kg). These treatments caused a significant increase in the sensitivity of hypothalamic synaptosomes to the inhibitory action of the noradrenergic agonist clonidine on the ³H-noradrenaline release elicited by K depolarization. Frontal cortex α2-autoreceptors were not affected by drug treatments. However, the ³H-p-aminoclonidine (³H-PAC) bindig to membranes from hypothalamus or frontal cortex from treated animals was the same as in controls. Changes in neural firing, elicited by the α2-antagonists on noradrenergic neurons, could explain our results. The presynaptic autoreceptors may thus become hypersensitive to counteract the enhanced neurotransmitter release in the hypothalamus, where the noradrenaline is accumulated at the synaptic cleft. In the frontal cortex, where it seems that only 5% of the noradrenergic terminals make synaptic contacts with postsynaptic elements, the α2-autoreceptors are less sensitive to an enhanced neurotransmitter release. Alternatively, they have scarce functional importance because the noradrenaline release is effectively modulated by the inhibitory recurrent locus coeruleus collaterals. At the postsynaptic level, the receptor down-regulation might be prevented by chronic presence of the antagonist drug. Thus the different behavior between pre- and postsynaptic α2-receptors and between α2-receptors of different brain areas may be ascribed to a different modulation rather than to different molecular arrangements.