Circadian activation of the hypothalamic–pituitary–adrenal axis may affect central, but not peripheral, effect of lithium in conditioned taste aversion learning in rats

Abstract Activation of the hypothalamic–pituitary–adrenal (HPA) axis has been implicated in conditioned taste aversion (CTA) learning induced by lithium chloride. This study investigated if circadian activation of the HPA axis affects the lithium-induced CTA formation. The pairing of conditioned stimulus (sucrose) and unconditioned stimulus (lithium chloride) was performed at night (shortly after light-off) when the HPA activity shows its circadian increase. Intraperitoenal injection of lithium chloride (0.15 M, 3 ml/kg or 12 ml/kg) at night induced CTA formation and the HPA axis activation and increased c-Fos expression in both the parabrachial nucleus (PBN) and the nucleus tractus of solitarius (NTS) in a dose dependent manner. However, intracerebroventricular lithium (0.6 M, 5 µl) at night failed to induce CTA or the HPA axis activation, although it increased c-Fos expression in the PBN and NTS. Results suggest that circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA formation, and the lithium-induced c-Fos expression in brain regions may not be effective to induce CTA unless it is coupled with the HPA axis activation. It is concluded that the HPA axis activation may play an important role mediating not only peripheral but also central effect of lithium in CTA formation.