RAT-BRAIN ALPHA-2-PRESYNAPTIC AND POSTSYNAPTIC RECEPTORS ARE DIFFERENT OR DIFFERENTLY MODULATED

In order to get better characterization of .alpha.2-pre- and postsynaptic noradrenergic receptors in the rat brain, we investigated the .alpha.2-receptor changes which take place during a 12-day treatment with the .alpha.2-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 .alpha.2-autoreceptors were not affected by drug treatments. However, the 3H-p-aminoclonidine (3H-PAC) binding to membranes from hypothalamus or frontal cortex from treated animals was the same as in controls. Changes in neural firing, elicited by the .alpha.2-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 is seems that only 5% of the noradrenergic terminals make synaptic contacts with postsynaptic elements, the .alpha.2-autoreceptors are less sensitive to an enhanced neurotransmitter release. Alternatively, they have scarce functional importance bacause 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 .alpha.2-receptors and between .alpha.2-receptors of different brain areas may be ascribed to a different modulation rather than to different molecular arrangements.