Modulating Action of an α2Adrenoreceptor Agonist, Clonidine, on Neuronal Activity and Synaptic Transmission in the Rat Prefrontal Cortex

Abstract

We studied the action of an α2-adrenoreceptor agonist, clonidine, on impulse activity of neurons of the prefrontal cortex (FRA; the cortical region playing an important role in cognitive processes). The background activity of such neurons and their responses to stereotaxic stimulation of the mediodorsal thalamic nucleus, MDM, directly projecting to FRA were recorded. Clonidine was applied microiontophoretically (50 mM, currents 5 to 40 nA, duration 20 to 30 sec). Applications of clonidine exerted ambivalent effects. A predominantly inhibitory action was manifested at small doses of the agent (currents about 5 nA). The frequency of background activity generated by FRA neurons and reactions of the latter to stimulation of afferent inputs from the thalamic nucleus decreased. With increase in the dose (currents 20-30 nA), the inhibitory effect of clonidine was usually replaced by excitation. These findings may help in the interpretation of a possible mechanism of psychopathological symptoms frequently observed when using α2-adrenoreceptor agonists in the treatment of drug addictions; these results emphasize the necessity of accurate selection of effective doses of such agents.