PSYCHOMOTOR STIMULANTS VERSUS ANTIDEPRESSANTS IN THE LEARNED HELPLESSNESS MODEL OF DEPRESSION

Animal models of depression which use stress to induce abnormal behavior generally cannot discriminate antidepressants from drugs which are central stimulants and predominantly stimulate dopamine (DA) neurons. Thus these models lack pharmacological specificity. The present study shows that the Learned Helplessness (LH) model, applied to Wistar rats, becomes a more valid pharmacological model if registration of the animals' behavior during the interval between each trial of the LH shuttlebox test is added. The DA drugs amphetamine, methylphenidate, nomifensine, apomorphine, quinpirole (specific D2 agonist), SKF 81297 (specific D1 agonist), and the antidepressants imipramine, amitriptyline, and isocarboxazide were tested. The results show that the DA drugs had an acute effect and increased the number of shuttle box crossings in the intervals between the test trials. The antidepressants had no acute effect and did not increase the number of intertrial crossings in the therapeutic dose range. The LH model thus seems to be advantageous when discrimination between drugs with DA psychomotor stimulating properties and drugs with antidepressant properties is needed.