Nitric oxide modulates retention of immobility in the forced swimming test in rats

Although originally developed as a possible screen for antidepressants, the Porsolt forced swimming test has more recently been extensively used as a model for studying the involvement of the endocrine system in the acquisition and retention of behavioural responses. In previous studies we have shown that while adrenalectomised rats acquire the immobile response normally, they are unable to retain it on retest next day. In the present study we show that retention of the immobile response in the Porsolt swim test is impaired in intact rats given the nitric oxide (NO) inhibitor L-N-arginine methyl ester (L-NAME), in a dose- and time-dependent manner. At a dose of 50 mg/kg levels of immobility are similar to those in adrenalectomised animals, an effect reversed by the simultaneous administration of L-arginine (50 mg/kg). L-Arginine also reverses the behavioural effect of adrenalectomy, and L-NAME blocks the ability of dexamethasone or the kappa-selective opioid ketocyclazocine to reverse the effect of adrenalectomy on retention of the immobile response. We conclude that the kappa-opioid and glucocorticoid mediated pathways previously shown to independently facilitate retention are mediated by nitric oxide.