Footshock-induced changes in brain catecholamines and indoleamines are notmediated by CRF or ACTH

Stressful treatments have long been associated with increased activity of b rain catecholaminegic and serotonergic neurons. An intracerebroventricular (icv) injection of the corticotropin-releasing factor (CRF) also activates brain catecholaminergic neurons. Because brain CRF-containing neurons appea r to be activated during stress, it is possible that CRF mediates the catec holaminergic activation. This hypothesis has been tested by assessing the r esponses in brain catecholamines and indoleamines to footshock in mice pret reated icy with a CRF receptor antagonist, and in mice lacking the gene for CRF (CRFko mice). Consistent with earlier results, icy administration of C RF increased catabolites of dopamine and norepinephrine, but failed to alte r tryptophan concentrations or serotonin catabolism. A brief period of foot shock increased plasma corticosterone and the concentrations of tryptophan and the catabolites of dopamine, norepinephrine and serotonin in several br ain regions. Mice injected icy with. 25 mu g alpha-helical CRF9-41 prior to footshock had neurochemical responses that were indistinguishable from con trols injected with vehicle, while the increase in plasma corticosterone wa s slightly attenuated in some experiments. CRFko mice exhibited neurochemic al responses to footshock that were indistinguishable from wild-type mice. However, whereas wild-type mice showed the expected increase ia plasma cort icosterone, there was no such increase in CRFko mice. Similarly, hypophysec tomized mice also showed normal neurochemical responses to footshock, but n o increase in plasma corticosterone. Hypophysectomy itself elevated brain t ryptophan and catecholamine and serotonin metabolism. Treatment with ACTH i cv or peripherally failed to induce any changes in cerebral catecholamines and indoleamines. These results suggest that CRF and its receptors, and ACT H and other pituitary hormones, are not involved in the catecholamine and s erotonin responses to a brief period of footshock. (C) 2000 Elsevier Scienc e Ltd. All rights reserved.