Abstracts

The cingulate cortex is a major anatomical component of the limbic system, surrounding the corpus callosum throughout its extent. Through its numerous and complex connections within and beyond the limbic system, the cingulate cortex plays different physiological roles that make of it an eclectic structure. According to Vogt et al. (Science 1979; 204:205-207; Vogt et al., Cereb Cortex, 1992; 2:435-443) two main subdivisions can be identified within the cingulate cortex: the anterior cingulate cortex (ACC) and the posterior cinguate cortex (PCC), the first being characterized by a high density of opioid receptors (Vogt et al., Exp Neurol, 1995; 135:83-92). To date, many studies have focused on the role of the ACC in pain, but little is known about its involvement in epilepsy. Here we investigate the role of mu-opiod receptors, which are capable of hyperpolarizing interneurons (Tanaka and North, J Neurosci, 1994; 14: 1106-1113), in the control of epileptiform activity in an [italic]in vitro[/italic] rodent model of epilepsy., Field potential recordings were obtained from ACC deep layers in coronal slices of adult rat brains. 4-aminopyridine (4AP) 50 uM was bath-applied for [ge] 1 hour to induce epileptiform activity. Drugs were bath-applied., 4AP-induced epileptiform activity was characterized by prolonged ictal-like discharges (mean duration= 35.2[plusmn]4.4 s, mean interval= 310.1[plusmn]34.2 s; n= 9) that were preceded by a slow negative-going event. Ictal-like activity was reversibly abolished by the NMDA receptor antagonist 6-cyano-7-nitroquino-xaline-2,3-dione (CPP, 10uM) and turned into brief epileptiform events (mean duration= 2.6[plusmn]0.1 s, mean interval 15.2[plusmn]1.9 s; n= 3) when GABAergic system was blocked by picrotoxin 50uM plus CGP 55845 4uM, GABAA and GABAB receptor antagonists respectively. [D-ala2, N-Me-Phe4,Gly5-ol]-enkephalin (DAGO) 10 uM, a mu-opioid receptors agonist, decreased and eventually abolished ictal-like discharges. This effect was reversed by naloxone 10 uM, an opioid antagonist. Finally, DAGO had no apparent effect on the brief epileptiform discharges recorded after GABAergic system blockade., These results suggest that the ACC is capable of generating epileptiform discharges that primarily depend on NMDA receptors activation. In addition they suggest that opioid receptors may play a critical role in controlling seizures. This action may be mediated via modulation of GABAergic interneuron activity., (Supported by CIHR (Grant 8109), CURE and the Savoy Foundation.)