NKH-477 is a water-soluble analogue of forskolin that stimulates adenylate cyclase and has antidepressant properties in the forced swim model of depression. The effect of chronic NKH-477 on locomotion and rearing and its behavioural interaction with lithium and inositol was tested. NKH-477 (1.5 mg/kg), administered acutely or chronically for 9 d to rats, induced a signficant reduction in locomotor behaviour and rearing. In a second experiment, rats were pretreated with chronic dietary lithium, inositol or control diet for 3 wk before being injected with either saline or NKH-477. Inositol had no effect on the decreased locomotion and rearing induced by NKH-477. There was a significant, but transient, interaction between lithium and NKH-477 on rearing on the second and third days of treatment. The lithium group had lower baseline rearing than control or inositol-treated rats, and was not further affected by NKH-477 treatment. This is the first report of a marked effect of this forskolin analogue on locomotion and rearing, with no tolerance in the time frame examined. The interaction between NKH-477 and lithium suggests that the well-documented ability of lithium to inhibit stimulation of the cAMP system is relevant to its behavioural effects; however, the transient nature of this interaction, suggests that other biochemical mechanisms are involved in the behavioural effects of lithium.
- Cyclic AMP
- Locomotor activity