Neurochemical and behavioral correlates of antidepressant drug action.

Chronic (4 days or more) administration of imipramine or mianserin, but not atropine, leads to an extinction in muricidal behavior in the rat. Moreover, receptor binding assays revealed that there is a significant decline in the number of beta-adrenergic, but not serotonin2, receptors in the frontal cortex at the onset of the behavioral modification. While the antidepressants also induced receptor binding changes in nonmuricidal control animals, the pattern of these changes differed from that observed in the muricidal subjects suggesting that the receptor modification was, to some extent, trait-dependent. These findings indicate that, with the muricidal model, chronic rather than acute drug treatment may be a more selective test for antidepressant efficacy. In addition, the data suggest that a decline in brain beta-adrenergic receptors may be causily related to the behavioral modification.