A behavioral and autonomic nervous system study of chronic imipramine administration to conscious dogs

The clinically effective antidepressant imipramine, an iminodibenzyl structure, was examined in two experimental methods which had previously demonstrated high prediction ability in descerning and categorizing potential psychotherapeutic drugs. The chronic administration of imipramine produced a significant reduction in the scores of aberrant behavioral response evoked by the fixed-dose with Ditran seen as early as 1 week after treatment was initiated and continuing through the 8-week treatment duration. This chronic per oral treatment with impramine was also associated with a significant potentiation of mean arterial pressure responses to fixed-dose treatment with serotonin, noradrenaline, yohimbine and adrenaline, while significantly inhibiting the histamine-induced depressor response. The results of this study support the speculation that, in dogs, the clinically effective antidepressants antagonize or reverse the Ditran-induced response and produce an associated response of sympathetic nervous system arousal or sensitization.