Depression of LTP in Rat Dentate Gyrus by Naloxone is Reversed by GABAA Blockade

Long-term potentiation (LTP) of the lateral perforant path (LPP) to dentate granule cell (DGC) synapse is suppressed by the opioid antagonist, naloxone, and thus appears to be dependent upon the release of endogenous opioids from the LPP. It has been suggested that endogenous opioids enhance LTP by depressing GABAA inhibition. As one test of this hypothesis, we determined whether blockade of GABAA inhibition would alleviate the naloxone block of LTP in the LPP. Consistent with the hypothesis that endogenous opioids enable LTP by disinhibition of the DGCs, naloxone no longer blocked LTP in the presence of the GABAA antagonist, bicuculline methiodide. Furthermore, although blockade of mu receptors suppressed LTP of the slope of the population excitatory potential (pEPSP), blockade of both mu and delta opioid receptors was needed to suppress LTP of both the pEPSP and the orthodromic population spike (OPS).