Opioid actions on neurons of rat lateral amygdala in vitro.
Intracellular recordings were made from neurons in the lateral nucleus of the amygdala, in a slice of rat brain that was superfused in vitro. [Met5]enkephalin (3-30 microM) and the mu receptor selective agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol; 0.3-3 microM) hyperpolarized about 50% of cells; this was blocked by naloxone and by the mu receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). The pA2s for naloxone and CTOP were 8.3 and 7.7, respectively. DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen: delta receptor selective) and U50488 (trans-(+-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate; kappa receptor selective) had no effect. Synaptic potentials mediated by gamma-aminobutyric acid (GABA) acting at GABAA receptors were elicited by focal stimulation of the slice in a combination of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (10 microM) and 4-aminophosphonovaleric acid (30 microM). They were inhibited by up to 60% by DAMGO and by DPDPE. The action of DAMGO was blocked by CTOP but not by the delta-selective antagonist ICI174864 (N,N-bisallyl-Tyr-Aib-Aib-Phe-Leu-OH, Aib = aminoisobutyrate). The action of DPDPE was blocked by ICI174864 but not by CTOP. Depolarizations elicited by addition of GABA to the superfusing solution were not affected by opioids. It is concluded that activation of mu opioid receptors hyperpolarizes about 50% of lateral amygdala neurons. Activation of either mu or delta receptors also inhibits presynaptically the release of GABA.
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Vollum Institute, Oregon Health Sciences University, Portland 97201.
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects
D000596:Amino Acids; D000700:Analgesics; D004745:Enkephalins; D058787:GABA-A Receptor Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D011759:Pyrrolidines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; D013004:Somatostatin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine