title: Neuroadaptation of GABAergic transmission in the central amygdala during chronic morphine treatment.
abstract: We investigated possible alterations of pharmacologically-isolated, evoked GABA(A) inhibitory postsynaptic potentials (eIPSPs) and miniature GABA(A) inhibitory postsynaptic currents (mIPSCs) in the rat central amygdala (CeA) elicited by acute application of µ-opioid receptor (MOR) agonists (DAMGO and morphine; 1 µM) and by chronic morphine treatment with morphine pellets. The acute activation of MORs decreased the amplitudes of eIPSPs, increased paired-pulse facilitation (PPF) of eIPSPs and decreased the frequency (but not the amplitude) of mIPSCs in a majority of CeA neurons, suggesting that acute MOR-dependent modulation of this GABAergic transmission is mediated predominantly via presynaptic inhibition of GABA release. We observed no significant changes in the membrane properties, eIPSPs, PPF or mIPSCs of CeA neurons during chronic morphine treatment compared to CeA of naïve or sham rats. Superfusion of the MOR antagonist CTOP (1 µM) increased the mean amplitude of eIPSPs in a majority of CeA neurons to the same degree in both naïve/sham and morphine-treated rats, suggesting a tonic activation of MORs in both conditions. Superfusion of DAMGO decreased eIPSP amplitudes and the frequency of mIPSCs equally in both naïve/sham and morphine-treated rats but decreased the amplitude of mIPSCs only in morphine treated rats, an apparent postsynaptic action. Our combined findings suggest the development of tolerance of the CeA GABAergic system to inhibitory effects of acute activation of MORs on presynaptic GABA release and possible alteration of MOR-dependent postsynaptic mechanisms that may represent important neuroadaptations of the GABAergic and MOR systems during chronic morphine treatment.
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Bajo
authors.forename: Marisa
authors.initials: M
authors.lastname: Roberto
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Madamba
authors.forename: George Robert
authors.initials: GR
authors.lastname: Siggins
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D009294:Narcotics; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D009020:Morphine