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 5HT2 receptors, and hippocampal 5HT1A receptors were studied (using the ligands [3H]-dihydroalprenolol, [3H]-ketanserin and [3H]-8-OH-DPAT, respectively), following 7 weeks of CMS and 4 weeks of imipramine treatment (10 mg/kg per day). CMS increased Bmax for all three receptor systems. Imipramine decreased Bmax, reversing the effect of CMS, for beta-adrenergic and 5HT2 receptor binding, but increased Bmax for 5HT1A receptor binding. KDs were unaffected by either treatment. The beta-receptor and 5HT2 receptor binding data are consistent with accounts of antidepressant action derived from studies in normal animals, but the 5HT1A receptor binding data are more difficult to reconcile. In no case was there a good correlation between receptor binding and behavioural data.
Papp
M
M
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Klimek
V
V
Willner
P
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000378:metabolism* / Q000523:psychology; D004082:Dihydroalprenolol; D007099:Imipramine / Q000494:pharmacology*; D007650:Ketanserin; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D004082:Dihydroalprenolol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D007099:Imipramine