THE MECHANISM OF ACTION OF ALPHA(2) ADRENOCEPTOR BLOCKERS AS REVEALEDBY EFFECTS ON OPEN-FIELD LOCOMOTION AND ESCAPE REACTIONS IN THE SHUTTLE-BOX

The precise mechanism of action of alpha(2) adrenoceptor blockers is n ot known, although in principle they have two main effects: (i) they s timulate the norepinephrinergic system by inhibiting the negative feed back of norepinephrine release (presynaptic effect) and (ii) they inh ibit the effects of norepinephrine on postsynaptic alpha(2) adrenocept ors. We postulate that if the presynaptic actions of the antagonists p revail, the enhanced norepinephrine release leads to an activation of postsynaptic alpha(1) or beta adrenoceptors. In this case the effects of alpha(2) adrenoceptor blockers can be reversed by antagonists actin g on the latter two adrenoceptors, since postsynaptic at adrenoceptors are also blocked. If the postsynaptic blockade of alpha(2) adrenocept ors is the main cause of effects, than the blockade of alpha(1) or bet a adrenoceptors should not reverse the action of alpha(2) blockers. Th e alpha(2) blocker idazoxan (dose 0.5-5 mg/kg) increased locomotor act ivity in an open field, an effect that was abolished by both alpha(1) and beta receptor blockers (prazosin and propranolol, respectively). E scape responses in a shuttle box were strongly suppressed by idazoxan (0.5-2 mg/kg). However, this effect was not changed by concomitant alp ha(1) or beta receptor blockade. These results suggest that the mechan ism of action of alpha(2) adrenoceptor blockers depends on which effec ts are studied. Exploration seems to be affected by a presynaptic mech anism as neurons bearing postsynaptic alpha(1) or beta adrenoceptors a re involved in the control of this behavior, while escape reactions ap pear to be affected by the postsynaptic blockade of alpha(2) adrenocep tors (i.e. neurons bearing postsynaptic alpha(2) adrenoceptors are inv olved in its control). Thus, there is no generalized mechanism of acti on for ar, adrenoceptor blockers; their precise mode of action should be investigated in each particular case.