Active behaviours produced by antidepressants and opioids in the mouse tail suspension test

Most classical preclinical tests to predict antidepressant activity were initially developed to detect compounds that influenced noradrenergic and/or serotonergic activity, in accordance with the monoaminergic hypothesis of depression. However, central opioid systems are also known to influence the pathophysiology of depression. While the tail suspension test (TST) is very sensitive to several types of antidepressant, the traditional form of scoring the TST does not distinguish between different modes of action. The present study was designed to compare the behavioural effects of classical noradrenergic and/or serotonergic antidepressants in the TST with those of opioids. We developed a sampling technique to differentiate between behaviours in the TST, namely, curling, swinging and immobility. Antidepressants that inhibit noradrenaline and/or serotonin re-uptake (imipramine, venlafaxine, duloxetine, desipramine and citalopram) decreased the immobility of mice, increasing their swinging but with no effect on their curling behaviour. No differences were observed between antidepressants that act on noradrenergic or serotoninergic transmission. While opioid compounds also decreased the immobility of the mice [morphine, codeine, levorphanol, (-)-methadone, (±)-tramadol and (+)-tramadol], they selectively increased curling behaviour. Blocking opioid receptors with naloxone prevented the antidepressant-like effect of codeine, and μ-opioid receptor knockout decreased normal curling behaviour and blocked (±)-tramadol-induced curling, further demonstrating the reliability and validity of this approach. These results show that at least two behaviourally distinct processes occur in the TST, highlighting the antidepressant-like effects of opioids evident in this test. Furthermore, our data suggest that swinging and curling behaviours are mediated by enhanced monoamine and opioid neurotransmission, respectively.