Differential actions of diazepam and zolpidem in basolateral and central amygdala nuclei.
Benzodiazepines are among the most widely prescribed therapeutic agents, having anxiolytic, anticonvulsant, sedative/hypnotic, and amnestic properties (Mehta and Ticku, Brain Res. Rev. 29 (1999) 196). Recent research indicates that these disparate actions are dissociable (Nature 401 (1999) 796; Science 290 (2000) 131; Kralic et al., Neuropharmacology 43 (2002) 685). Behavioral studies indicate that the amygdala plays a critical role in the anxiolytic effect of benzodiazepines (Nagy et al., Neuropharmacology 18 (1979) 573; The amygdala: anxiety and benzodiazepines. The Amygdala: a Functional Analysis. p. 195). However, the neuronal substrates of this anxiolytic effect remain unclear. Our study characterizes the physiological response to acute application of the benzodiazepine diazepam and the non-benzodiazepine sedative zolpidem using whole cell patch recording in two discrete amygdala subnuclei. We found that acute application of diazepam enhances GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) with equal potency in the basolateral (BL) and central (Ce) amygdala subnuclei. However, zolpidem enhanced IPSCs with similar potency only in the BL, and was effective in the Ce only at high concentrations. This finding is in agreement with histochemical data regarding the localization of GABA(A) receptor isoforms in the amygdala (J. Comp. Neurol. 359 (1995) 154; Brain Res. 964 (2003) 91) and suggests that anxiolytic effects of allosteric modulators of the GABA(A) receptor may be further dissociated from their hypnotic/sedative effects.
Kang-Park
M-H
MH
Department of Molecular Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Wilson
W A
WA
Moore
S D
SD
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000528:radiation effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011725:Pyridines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077334:Zolpidem
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D011725:Pyridines; D011810:Quinoxalines; C017069:bicuculline methiodide; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D000077334:Zolpidem; D014633:Valine; D003975:Diazepam; D001640:Bicuculline