Chronic, combined treatment with desipramine and mianserin: enhanced 5-HT1A receptor function and altered 5-HT1A/5-HT2 receptor interaction in rats

A greater percentage of depressed patients respond to combined treatment with a tricyclic antidepressant and the tetracyclic antidepressant mianserin than to treatment with these drugs given alone. The functional sensitivity of the 5-hydroxytryptamine (5-HT)1A receptor, and the functional interaction between the 5-HT1A and the 5-HT2 receptors were investigated after treatment with desipramine and mianserin either alone or combined for 21-28 days. Pretreatment with desipramine and mianserin in combination induced the most intense 5-HT syndrome and the greatest fall in colonic temperature after injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT). The rats pretreated with desipramine alone had the largest elevation of the response temperature in the increasing temperature hot-plate test after injection of 8-OH-DPAT. After the combined pretreatment with desipramine and mianserin, no enhanced functional response in these tests was found when the 5-HT1A and the 5-HT2 receptors were stimulated simultaneously using 8-OH-DPAT and the 5-HT2 agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), contrasting the findings for desipramine or mianserin treatments given alone, where an increased functional response was found for the colonic temperature and the response temperature in the increasing temperature hot-plate test. In vitro receptor binding using [3H]-8-OH-DPAT as ligand revealed an increase in Kd and Bmax in the spinal cord after chronic treatment with the combination of desipramine and mianserin. In the hippocampus and the frontal cortex the changes were small.(ABSTRACT TRUNCATED AT 250 WORDS)