Minocycline alleviates behavioral deficits and inhibits microglial activation induced by intrahippocampal administration of Granulocyte–Macrophage Colony-Stimulating Factor in adult rats

Abstract

Some evidence has shown an increased number of activated microglial cells in patients with schizophrenia. It is hypothesized that activated microglia may contribute to the pathogenesis of schizophrenia. We injected saline or Granulocyte–Macrophage Colony-Stimulating Factor (GM-CSF) into the ventral hippocampus in adult Sprague–Dawley rats via micro-pump; at the same time, the rats were intragastrically administrated with saline or minocycline once a day for 14 consecutive days. Then, behavioral tests were examined and microglia were assessed using immunohistochemistry method. GM-CSF-injected group showed significant behavioral deficits (hyperlocomotion, social interaction deficits, prepulse inhibition (PPI) deficits). There was a dramatic increase of the number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared with those in saline-injected group in immunohistochemistry. Minocycline was able to ameliorate deficits of social interaction and PPI but not hyperlocomotion. Minocycline was also able to inhibit the microglial activation. In conclusion, intrahippocampal administration of GM-CSF in adult rats may serve as a potential schizophrenia animal model, which may be related with the microglia hypothesis of schizophrenia.