Further analysis of the specificity of a novel animal model of depression--effects of an antihistaminic, antipsychotic and anxiolytic compound.

In previous papers we reported that chronic stress elicited reductions in selected forms of open field activity resembled endogenomorphic depression upon behavioral, motivational, neuroendocrine, and neuropharmacological grounds. In particular, the loss of acute stress elicited activity proved to be exclusively reversible by antidepressant treatments. Insofar as clinically ineffective compounds were tested, the deficit proved refractory to treatment, further suggesting the model reflected just those processes which were disrupted in depression. A number of ineffective compounds are known to yield false positives upon other related tests, but have yet to be examined in the present model. Three such compounds, an antihistamine (tripelennamine), a neuroleptic (haloperidol), and an anxiolytic (oxazepam) were examined for their behavioral and neuroendocrine effects. Although other stress related phenomena were replicated, none of the above compounds was effective in restoring the activation deficit or in eliminating the endocrine abnormality. This suggests the depression model is relatively selective pharmacologically and not critically dependent upon receptor blocking properties of the above drugs.