The mechanism of disinhibition produced by opioid peptides was studied using intracellular recording in area CA1 of rat hippocampal slices. The μ-selective opioid peptide [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO) reversibly depressed directly-activated, monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and d,l-2-amino-5-phosphonovalerate (APV) in a naloxone-sensitive manner. Depression of monosynaptic inhibitory postsynaptic potentials (IPSPs) by DAGO was not prevented by 1-2 mM Ba2+. DAGO reversibly depressed monosynaptic IPSPs when applied locally close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that DAGO disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating μ opiate receptors located on the terminals of inhibitory neurons, and by a Ba2+-insensitive mechanism.
- Opioid peptide
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