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 c onscious mice is a simple and useful technique for studying the centra l actions of drugs in mice. However, the use of this technique to diss ect the central regulatory mechanisms of stress-activated hypothalamo- pituitary-adrenocortical (HPA) axis may produce confusing results diff icult to interpret, because i.c.v. injection itself induces an increas e 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 str ess stimulus in mice. An i.c.v. saline injection induced an increase i n plasma corticosterone levels in mice, which reached a maximum of 38. 0 +/- 1.9 mu g/100 ml at 30 min after the i.c.v. injection. alpha-Heli cal corticotropin-releasing factor (CRF) 9-41, a CRF antagonist, injec ted i.c.v. (1, 3 mu g), effectively inhibited the injection stress-ind uced rise in plasma corticosterone levels, suggesting the involvement of CRF in this response. This i.c.v. injection stress model permits th e evaluation of the effects of drugs administered i.c.v. simultaneousl y. (C) 1998 Elsevier Science Inc.