Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain

The aim of the present study was to examine the effect of chronic tricyclic antidepressants (TCAs) treatment on the density of -adrenoceptors in the rat brain. Density of ₁- and ₂-adrenoceptors was measured in cortex and hippocampus of rats treated with imipramine (IMI, 5 mg/kg body weight), desipramine (DMI, 10 mg/kg body weight), clomipramine (CMI, 10 mg/kg body weight) and amitriptyline (AMI, 10 mg/kg body weight), for 40 days, using ³H]prazosin and ³H]clonidine, respectively. The density of cortical ₁-adrenoceptors was significantly decreased with IMI (46%), DMI (21%), CMI (50%) and AMI (67%) treatment, without altering the affinity of the receptor. The density of cortical ₂-adrenoceptors was also significantly decreased with DMI (69%), CMI (81%) and AMI (80%) treatment, without affecting the affinity for ³H]clonidine. The density of hippocampal ₁-adrenoceptors was significantly decreased only with AMI treatment (47%), without affecting the affinity for ³H]prazosin. However, no change in hippocampal ₂-adrenoceptor density was observed with any of these TCAs. The results suggest that chronic antidepressant (AD) treatment downregulates the cortical, but not hippocampal, ₁- and ₂-adrenoceptors in rat brain. The region-specific downregulation of ₁- and ₂-adrenoceptors density, which occur after prolonged AD treatment, may underline the therapeutic mechanism of action.