Mu opioid receptor activation reduces inhibitory postsynaptic potentials in hippocampal CA3 pyramidal cells of rat and guinea pig.
Using intracellular recording techniques, we characterized synaptic responses of CA3 pyramidal cells to mu and kappa agonists in hippocampal slices from rats and guinea pigs. In rat CA3 pyramidal cells, the mu selective agonist (N-MePhe3,D-Pro4)-morphiceptin (PLO17) inhibited both the early and the late inhibitory postsynaptic potentials (IPSPs) and increased excitatory postsynaptic potential (EPSP) amplitudes. Voltage clamp analysis of synaptic currents indicated that the excitatory postsynaptic current were not increased by PLO17, showing that the apparent increase in EPSPs was a result of a decrease in the underlying IPSP. The kappa agonists trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate and dynorphin A (1-17) had no effect on EPSPs or IPSP conductances measured in rat pyramidal cells. Maximal inhibition of IPSPs by PLO17 resulted in a bursting response to stimulation in rat but not guinea pig CA3 pyramidal cells. In guinea pig CA3 pyramidal cells, PLO17 also inhibited IPSP conductances but did not affect EPSP amplitudes. In contrast to the lack of effect in rat pyramidal cells, trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate (100 nM) inhibited the late IPSP conductance without influencing the EPSP or the early IPSP conductance of guinea pig pyramidal cells. Dynorphin A (1-17) (0.01-10 microM) did not affect resting membrane properties or evoked synaptic conductances in either preparation. Mu receptor activationin the CA3 of rats and guinea pigs results in the inhibition of inhibitory synaptic input to pyramidal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Caudle
R M
RM
Department of Pharmacology, University of Washington, School of Medicine, Seattle.
Chavkin
C
C
D000818:Animals; D001345:Autoradiography; D004399:Dynorphins / Q000378:metabolism / Q000494:pharmacology; D004594:Electrophysiology; D004723:Endorphins / Q000378:metabolism / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D011712:Pyramidal Tracts / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013045:Species Specificity; D013569:Synapses / Q000187:drug effects
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004399:Dynorphins; C044708:morphiceptin, N-Me-Phe(3)-