PMID- 11713626 OWN - NLM STAT- MEDLINE DCOM- 20020111 LR - 20131213 IS - 0014-4819 (Print) IS - 0014-4819 (Linking) VI - 141 IP - 2 DP - 2001 Nov TI - Epileptiform activity in the nucleus accumbens induced by GABA(A) receptor antagonists in rat forebrain slices is of cortical origin. PG - 146-52 AB - Extracellularly recorded field potentials, evoked by stimulation of cortico-nucleus accumbens border, were recorded in the nucleus accumbens (NAcc) in horizontal slices of rat ventral forebrain. The field excitatory postsynaptic potential (EPSP) event (N2) was calcium dependent, blocked by tetrodotoxin (1 microM), and reduced by over 70% by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM), the antagonist of AMPA-type glutamate receptors. The EPSP amplitude was enhanced by either of the GABA(A) receptor antagonists, picrotoxin (10 microM; by 252+/-33%, n=18) and bicuculline methiodide (20 microM; by 216+/-34%, n=4). Additionally, picrotoxin (3-50 microM) and bicuculline methiodide (20 microM) promoted epileptiform activity within the NAcc, manifest as the emergence of additional late components, N3, N4 and N5, in the evoked synaptic waveform. In slices with the frontal cortex removed, picrotoxin (10-50 microM) and bicuculline methiodide (20 microM) were unable to promote epileptiform activity within the NAcc, although a smaller increase in the peak amplitude of the field EPSP (163+/-18%, n=6) was observed at the highest concentrations of picrotoxin (50 microM). Histological examination of the slice demonstrated that in such decorticated slices, the piriform cortex (PC) had been removed. We propose that stimulation of the cortico-NAcc border not only evokes an orthodromic EPSP in the NAcc, but also causes antidromic activation of cortical tissue. Disinhibition by GABA(A) antagonists of circuits intrinsic to the cortex, possibly the piriform cortex, is the principal cause of the facilitation of the EPSP and of regenerative epileptiform activity in NAcc evoked by stimulation of cortical input. FAU - Buckby, L E AU - Buckby LE AD - Department of Pharmacology, Division of Neuroscience, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK. FAU - Lacey, M G AU - Lacey MG LA - eng PT - Journal Article PL - Germany TA - Exp Brain Res JT - Experimental brain research JID - 0043312 RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (GABA Antagonists) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Receptors, AMPA) RN - 0 (Receptors, GABA-A) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 3KX376GY7L (Glutamic Acid) SB - IM MH - Animals MH - Cerebral Cortex/cytology/drug effects/*metabolism MH - Cerebral Decortication MH - Electric Stimulation MH - Epilepsy/chemically induced/metabolism/*physiopathology MH - Excitatory Amino Acid Antagonists/pharmacology MH - Excitatory Postsynaptic Potentials/drug effects/*physiology MH - GABA Antagonists/pharmacology MH - GABA-A Receptor Antagonists MH - Glutamic Acid/metabolism MH - Male MH - Neural Inhibition/drug effects/*physiology MH - Neural Pathways/cytology/drug effects/*metabolism MH - Neurons/drug effects/metabolism MH - Nucleus Accumbens/cytology/drug effects/*metabolism MH - Rats MH - Rats, Wistar MH - Receptors, AMPA/antagonists & inhibitors/metabolism MH - Receptors, GABA-A/*metabolism MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism MH - Synaptic Transmission/drug effects/*physiology EDAT- 2001/11/20 10:00 MHDA- 2002/01/12 10:01 CRDT- 2001/11/20 10:00 PHST- 2001/01/31 00:00 [received] PHST- 2001/06/13 00:00 [accepted] PHST- 2001/11/20 10:00 [pubmed] PHST- 2002/01/12 10:01 [medline] PHST- 2001/11/20 10:00 [entrez] AID - 10.1007/s002210100841 [doi] PST - ppublish SO - Exp Brain Res. 2001 Nov;141(2):146-52. doi: 10.1007/s002210100841.