EFFECTS OF IMIPRAMINE ON SEROTONERGIC AND BETA-ADRENERGIC-RECEPTOR BINDING IN A REALISTIC ANIMAL-MODEL OF DEPRESSION

Chronic exposure to mild unpredictable stress (CMS) has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions. In the present study, in addition to confirming these behavioural observations, the binding properties of cortical beta-adrenergic and 5HT(2) receptors, and hippocampal 5HT(1A) receptors were studied (using the ligands [H-3]-dihydroalprenolol, [H-3]-ketanserin and [H-3]-8-OH-DPAT, respectively), following 7 weeks of CMS and 4 weeks of imipramine treatment (10 mg/kg per day). CMS increased B-max for all three receptor systems. Impramine decreased B-max, reversing the effect of CMS, for beta-adrenergic and 5HT(2) receptor binding, but increased B-max for 5HT(1A) receptor binding. K(D)s were unaffected by either treatment. The beta-receptor and 5HT(2) receptor binding data are consistent with accounts of antidepressant action derived from studies in normal animals, but the 5HT(1A) receptor binding data are more difficult to reconcile. In no case was there a good correlation between receptor binding and behavioural data.