Buspirone Ameliorates the Morphine Withdrawal-Induced Anxiety through Synaptic Ultrastructural Changes in Hippocampus of Rat

Abstract

Morphine administration causes long-lasting neural changes in the brain that underpin the behavioral abnormalities, and the relationship between structural changes and behavioral symptoms is obscure. In present study, the elevated plus-maze and transmission electron microscope were applied to validate the anxiety-like behaviors and synaptic ultrastructural changes in the hippocampi of rats among the morphine group (morphine administration only), the buspirone group (morphine plus buspirone administration) and the vehicle (saline treated only). As compared with the vehicle group, lower values of OE (times of entering into the open arms), OE% (percentage of entries into the open arms), OT (time spent in the open arms), OT% (percentage of time stayed in the open arms), Ns (surface density (Sv)/numerical density (Nv)) and S (surface area) of synapses were observed in the morphine group , but significantly, behavior higher scores of RR (rearing), HD (head-dipping), FBA (flat back approach), and higher Nv, Sv, PSD (postsynaptic density), LPT (length of postsynaptic thickening), WCJ (widths in synaptic cleft on junctions) and CCR (curvature of the cleft region) of synapses appeared in the morphine group. However, no significant differences in values of most of those parameters above were detected between the vehicle group and the buspirone group. These results supported that anxiety-like symptoms of rats significantly occurred to the rats after acute morphine withdrawal, but buspirone administration could reverse these indexes. It also proved that the appearance/disappearance of anxiety-related symptoms was related to the ultrastructural changes/reversibility of synapses in the hippocampus with morphine and buspirone administrations. So, it suggested that anxiety-related symptoms were modified in rats subjected to the synaptic ultrastructural changes in hippocampus by morphine acute withdrawal and were further rehabilitated by buspirone administration. It is helpful to pursue the effective therapeutic methods of morphine addiction.