The behavioural effects of the specific and selective α2-adrenoreceptor antagonists, idazoxan, efaroxan and RX811059, have been investigated in the rat. All three drugs induced periods of behavioural activation characterized by increased locomotion and exploration (rearing and hole dipping). However, these effects were only apparent in animals which were fully habituated to their environments and thus displayed low baseline activity. The behaviour observed lay within the normal range of activity and was not apparent under conditions when exploration was stimulated such as in a novel environment. α 2-Adrenoreceptor antagonist- induced activation was a weak response when compared with the intense and prolonged hyperactivity, in both novel and non-novel environments, induced by the amine releaser D- amphetamine. Possible mechanisms involving a direct action of noradrenaline at postsynaptic α 1-adrenoreceptors (subsequent to enhanced presynaptic α2-receptor feedback blockade) or an indirect action of α2-antagonists on dopamine function in mesolimbic pathways are discussed.
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