EFFECTS OF IDAZOXAN ON DOPAMINE RELEASE IN THE PREFRONTAL CORTEX OF FREELY MOVING RATS

To clarify the involvement of dopaminergic neuronal systems in anxiety or fear, the present study was undertaken to elucidate the effect of an anxiogenic agent, idazoxan, a selective alpha(2)-adrenoceptor antag onist, on dopamine release from the rat prefrontal cortex by use of in vivo microdialysis. Systemic administration of idazoxan (0.25 mg/kg, i.p.) produced significant increases in extracellular levels of dopami ne. The maximum response of the facilitatory effect of dopamine releas e was 241.5%, which was detected 80 min after the injection of idazoxa n. Idazoxan-induced (0.25 mg/kg, i.p.) increases in dopamine release w ere prevented by an established anxiolytic agent, diazepam (0.5 mg/kg, i.p.) and a putative anxiolytic agent tropisetron (100 mu g/kg, i.p.) . These results suggest that the excessive dopaminergic neuronal activ ity in the rat prefrontal cortex is related to idazoxan-induced anxiog enic effects. The idazoxan-induced (0.25 mg/kg, i.p.) enhancement of d opamine release was further prevented by pretreatment with serotonin ( 5-hydroxytryptamine; 5-HT) neurotoxin, 5,7-dihydroxytryptamine (200 mu g/kg, i.c.v.). The basal output of dopamine release was not altered i n 5-HT lesioned rats. These findings indicate that intact serotonergic neurons are required for the facilitatory effects of idazoxan on dopa mine release. In other words, the functional interaction between dopam inergic and serotonergic neuronal systems in the rat prefrontal cortex might be involved in anxiety or fear. (C) 1998 Elsevier Science B.V.