Inhibition of brain protein kinase C attenuates immobilization stress-induced plasma corticosterone levels in mice

To evaluate the involvement of brain protein kinase C (PKC) in the stress-i nduced activation of hypothalamic-pituitary-adrenal (HPA) axis, we examined the effects of PKC inhibitors administered intracerebroventricularly (i.c. v,) on the immobilization stress-induced plasma corticosterone levels in mi ce. Calphostin C (a pan-specific PKC inhibitor) injected i.c.v. decreased t he immobilization stress-induced plasma corticosterone level: maximal inhib ition of 35% was attained at a dose of 100 pmol. Go 6976 (an alpha and beta 1 PKC isotype-selective inhibitor) was less effective than Calphostin C: m aximal inhibition of 17% was attained at a dose of 30 pmol. Phorbol 12-myri state 13-acetate (a general PKC activator) injected i.c.v. at doses of 16 a nd 48 pmol increased the plasma corticosterone levels in a dose-dependent m anner. The present study demonstrates the involvement of PKC in the brain i n the regulation of the immobilization stress-induced stimulation of HPA ax is in vivo. (C) 2000 Published by Elsevier Science Ireland Ltd.