Accelerated kindling development in μ-opioid receptor deficient mice

The relevance of μ-opioid systems for central excitability and kindling related disturbed learning performance was underlined by investigations using μ-opioid receptor knockout mice. Mice lacking μ-opioid receptors showed an accelerated kindling development induced by the convulsant drug pentylenetetrazol. Blockade of δ-opioid receptors by naltrindole suppressing kindling development in wild-type animals led to a further acceleration of kindled seizure development in the knockout mice. Mice lacking μ-opioid receptors showed such a low learning performance in the shuttle box, that the kindling induced learning deficit as seen in wild-type mice was not detected. The results were discussed on the basis of receptor binding studies with regard to subtypes of glutamatergic receptors, δ-opioid and somatostatin receptors. An increase in glutamate and so-matostatin binding could contribute to the enhanced excitability in the-μ-opioid receptor knockout mice.