Neuropeptides modulate compound postsynaptic potentials in basolateral amygdala.
Previous behavioral studies have shown that neuropeptides intrinsic to the amygdala formation can alter fear and anxiety states. We have previously shown that the anxiogenic neuropeptide cholecystokinin (CCK) increases inhibitory neurotransmission in basolateral amygdala. We have since observed that CCK induces synchronized rhythmic activity composed of compound postsynaptic potentials (cPSPs). We have now further characterized these cPSPs by inducing cPSPs routinely in 5 mM extracellular K(+). CCK facilitated cPSP occurrence in a dose dependent manner in brain slices from both young and mature rats. The cPSPs were attenuated by glutamate receptor antagonists (NBQX or DL-AP5) or low concentrations of GABA(A) receptor antagonists (bicuculline methiodide (BMI), SR95531, or picrotoxin), but not by the GABA(B) receptor antagonist, CGP52432. Low concentrations of tetrodotoxin (TTX, 10 nM) also attenuated the cPSPs. The Na-K-2Cl cotransporter blocker, bumetanide (1 or 10 microM) also blocked the cPSPs. The anxiogenic neuropeptide corticotropin-releasing factor (CRF) facilitated cPSPs while anxiolytic neuropeptides (neuropeptide Y (NPY) and somatostatin) attenuated cPSPs. The benzodiazepine agonist diazepam dose-dependently modulated cPSPs. Mefloquine facilitated cPSPs within 10 min of application. We hypothesize that cPSPs are generated by positive feedback between a subset of interneurons and a subset of glutamatergic projection neurons.
Chung
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Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Moore
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SD
D000200:Action Potentials; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002414:Cations, Monovalent; D002712:Chlorides / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis; D008297:Male; D015767:Mefloquine / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D011188:Potassium / Q000134:cerebrospinal fluid; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology; D055366:Synaptic Potentials / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D002414:Cations, Monovalent; D002712:Chlorides; D009478:Neuropeptide Y; D009479:Neuropeptides; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D013004:Somatostatin; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D003975:Diazepam; D011188:Potassium; D015767:Mefloquine