Regional aspects of the delay of acquisition conditioned avoidance responding by chlorpromazine.

Chlorpromazine injected into the amygdala, septum, or caudate delayed the acquisition of a one-way active avoidance response. Injections into nine other brain areas were inactive. Following a standard dose of chlorpromazine at its ED50 for delaying avoidance acquisition, tissue levels of chlorpromazine from those animals displaying reduced acquisition were significantly higher in the caudate and amygdala than from animals not demonstrating a drug effect.

Tricyclic antidepressant drug action correlates with its tissue levels in anterior neocortex.

In the behavioral reversal of learned helplessness in the rat by imipramine, a strong correlation is found between "cure" of helplessness and drug level in anterior neocortex, the locus of drug action in this model of depression. This suggests that the delayed onset of therapeutic action of antidepressant drugs is due to the time required to achieve adequate drug levels at the site of their action.

Specificity of the learned helplessness model of depression.

The learned helplessness model of depression was tested for its responsiveness to several types of antidepressant therapies, and to a number of psychoactive drugs which are not effective in treating depression in humans. Chronic administration of tricyclic antidepressants (imipramine, desipramine, amitryptyline, nortryptyline, or doxepin), atypical antidepressants (iprindole or mianserin), monoamine oxidase inhibitors (iproniazid or pargyline), or electroconvulsive shock was effective in reversing learned helplessness. Chronic treatment with anxiolytics (diazepam, lorazepam, or chlordiazepoxide), neuroleptics (chlorpromazine or haloperidol) stimulants (amphetamine or caffeine), or depressants (phenobarbital or ethanol) was not.