Intracerebroventricular injection-induced increase in plasma corticosterone levels in the mouse: a stress model

The method of intracerebroventricular (i.c.v.) injection of drugs to conscious mice is a simple and useful technique for studying the central actions of drugs in mice. However, the use of this technique to dissect the central regulatory mechanisms of stress-activated hypothalamo-pituitary-adrenocortical (HPA) axis may produce confusing results difficult to interpret, because i.c.v. injection itself induces an increase in plasma corticosterone in mice due to the traumatic nature of the technique. Here we propose to use the i.c.v. injection itself as a stress stimulus in mice. An i.c.v. saline injection induced an increase in plasma corticosterone levels in mice, which reached a maximum of 38.0+/-1.9 microg/100 ml at 30 min after the i.c.v. injection. Alpha-helical corticotropin-releasing factor (CRF) 9-41, a CRF antagonist, injected i.c.v. (1, 3 microg), effectively inhibited the injection stress-induced rise in plasma corticosterone levels, suggesting the involvement of CRF in this response. This i.c.v. injection stress model permits the evaluation of the effects of drugs administered i.c.v. simultaneously.