394 Brain Research, 408 ( lq87~ 3t)4-39g f~lscvie~ BRE 22185 Different epileptogenic activities of murine and ovine corticotropin-releasing factor F. Marrosu l, G. Mereu 2, W. Fratta 2, P. Carcangiu 2, F. Camarri 2 and G.L. Gessa 2 1Institute of Neurology and 2Institute of Pharmacology, University of Cagliari, Cagliari (Italy) (Accepted 23 December 1986) Key words: Corticotropin-releasing factor (CRF); Epilepsy; Naloxone; Verapamil The behavioral and EEG effects of rat and ovine corticotropin releasing factor (r- and o-CRF) were compared. Both peptides were injected intracerebroventricularly into rats through chronically implanted cannulae. At the doses of 0.1 and 1 ~g both peptides acti- vated the EEG and stimulated motor activity. At the dose of 10 ~g they produced spiking activity. However, while o-CRF-induced spiking activity was present both in the hippocampus and in the cortical leads and was associated with generalized myoclonic move- ments, that induced by r-CRF was confined in the hippocampus and was not accompanied by myoclonic movements. Spiking activity induced by r-CRF was suppressed by verapamil, but was not influenced by naloxone. Experimental evidence suggests that corticotro- the rat peptide (r-CRF) in releasing ACTH from the pin-releasing factor (CRF) 15 controls not only the rat pituitary in vitro 12. release of adrenocorticotropin hormone (ACTH) Since, however, the two peptides differ in 7 ami- and fl-endorphin from pituitary 6'18 but also plays a noacid positions 12, it was of interest to compare their transmitter role in the central nervous system behavioral and EEG effects. Moreover, in order to (CNS) 1°. obtain some information about the possible role of In fact, in addition to CRF-immunoreactive neu- opioids and Ca 2+ in CRF action, the effect of nalox- rons projecting to the median eminence 14, a number one and verapamil on CRF-induced seizure activity of such neurons are widely but selectively distributed was studied. in different brain areas 4"18. CRF has predominantly Male Sprague-Dawley rats weighing 250-300 g, excitatory action on various neuronal populations, individually housed in a temperature controlled both in vivo and in brain slices )'5"19. Moreover the in- room, with 12 h light-dark cycle, were used. The ani- tracerebroventricular (i.c.v.) injection of CRF to mals were anesthetized with chloral hydrate (400 rats has been shown to produce EEG activation and mg/kg, i.p.). A 23-gauge stainless steel guide cannula epileptic activity 5. The latter is either restricted with- was lowered into a lateral ventricle (P 1.0, V 1.6, V in the amygdala and hippocampus or spreads from 4.6, Pellegrino-Cushman Atlas) and a dummy stylet these regions to cortical areas H3. was positioned into the cannula. Bipolar stainless- Associated with the electrographic seizure activi- steel electrodes were positioned in dorsal hippocam- ty, behavioral seizure activity has been observed, pus (P 3.5, V 2.2, V 3.3, bregma being the landmark) ranging from myoclonic movements to apparent loss and stainless-steel screw electrodes in the calvarium of consciousness 5. over the frontoparietal and parieto-occipital cortices. On the basis of these data, it has been suggested Electrodes were connected to a multi-pin connector that CRF might play an important role in epilepsy 5'2°. which was anchored to the skull with dental acrylic In the above studies the synthetic ovine peptide cement and stainless steel screws. The connection (o-CRF) has been used, which is equally potent to between the connector and the EEG machine was Correspondence." G.L. Gessa, Institute of Pharmacology, University of Cagliari, Via Porcell, 4, 09100 Cagliari, Italy. 0006-8993/87/$03.50 © 1987 Elsevier Science Publishers B .V. (Biomedical Division)