Effects of apomorphine on the expression of learned helplessness behavior

Dopaminergic system and its D1 as well as D2 receptors are involved in the modulation of emotional behavior. This experiment investigated the role of dopaminergic activity in the inescapable stress-induced learned helplessness, a widely used depression animal model, by using the pharmacological manipulation through the apomorphine (APO), an agonist for D1 and D2 receptors, and sulpiride (SUL), a selective D2 antagonist. Male Sprague Dawley rats were used and tested in a shuttle box. In the day-1 session, the rats received a 10-trial (1 min/trial) inescapable stressor: a 3 sec conditioned stimulus (CS; 75 db sound and 250 lux red light) followed by a 10 sec unconditioned stimulus (UCS; electrical foot shock, 0.5 mA). In the day-2 session, a 15-trial active avoidance test, 3 sec CS followed by UCS, was performed 30 min after the administration of APO (0, 0.05, 0.5, 1, and 5 mg/kg, i.p.). The number of failures was counted and the UCS was stopped when the rats did not escape after 15 sec UCS. The results showed that APO at the dosage of 0.5 mg/kg had a tendency to enhance the avoidance behavior. In contrast, the treatment of higher dose of APO, 1 and 5 mg/kg, reduced the number of escape but increased the number of failure. Pretreatment of SUL (5 mg/kg, i.p.), 10 min before 1 mg/kg of APO, significantly enhanced the failure behavior. The present data suggest that the activity of D2 receptor may be associated with the adaptive or protective role in the prevention of escape deficits after exposure to inescapable stress. However, the excessive stimulation of D1 receptor may participate in the failure of coping behavior leading to learned helplessness and therefore in the pathophysiological mechanisms underling the development of depression.