DISTINCT CHANGES IN PEPTIDE YY BINDING TO, AND MESSENGER-RNA LEVELS OF, Y1 AND Y2 RECEPTORS IN THE RAT HIPPOCAMPUS ASSOCIATED WITH KINDLINGEPILEPTOGENESIS

Electrical kindling of the rat dorsal hippocampus induced significant changes in the binding of I-125- peptide YY to Y1 and Y2 subtypes of n europeptide Y receptors and in their mRNA levels in the area dentata a s assessed by quantitative receptor autoradiography and in situ hybrid ization histochemistry. Binding to Y1 receptor sites decreased by 50% (p < 0.05) in the molecular layer of the stimulated dentate gyrus, 2 d ays after preconvulsive stage 2 and 1 week or 1 month after generalize d stage 5 seizures compared with sham-stimulated rats. Binding to Y2 r eceptor sites increased bilaterally by 36-87% (p < 0.05) in the hilus at stage 2 and 1 week or 1 month after stage 5, No significant changes were observed after one afterdischarge or in the other hippocampal su bfields or in the cortex. Y1 receptor mRNA signal decreased bilaterall y by 50-64% (p < 0.01) in the granule cell layer, 6 h but not 24 h aft er stages 2 and 5. The Y2 receptor mRNA signal was enhanced by 283% (p < 0.01) in the stimulated granule cell layer 24 h after stage 2, At 6 and 24 h after stage 5, mRNA levels were increased both ipsilaterally (283 and 360%, respectively; p < 0.01) and contralaterally (190 and 2 60%, respectively; p < 0.05). No significant changes in level of eithe r mRNA was found following one afterdischarge. These modifications, an d the enhanced neuropeptide Y release previously shown in the hippocam pus, suggest that kindling is associated with lasting changes in neuro peptide Y-mediated neurotransmission.