ABSTRACT
Objective To study the effects of 5-HT1A receptor in hippocampal dentate gyrus on anxiety behavior of adult rats with Parkinson's disease (PD).Methods PD model in rats was constructed by using 6-hydroxydopamine (6-OHDA) to lesion the medial forebrain bundle (MFB).In lesioned rats and sham-operated rats,we examined the changes of the number of TFH-positive neurons in the SNc and VTA.We also examined how 5-HT1A receptor of hippocampal dentate gyrus (DG) modulates the anxiety-related behavior using open field test and elevated plus-maze test,and examined monoamine neurotransmitter changes in the striatum,medial prefrontal cortex (mPFC),amygdale and ventral hippocampus using reverse-phase high performance liquid chromatography with electrochemical detection.Results In 6-OHDA-lesioned rats,the SNc of the injected side showed a total loss of TH-ir neurons compared with the unlesioned side,and the number of TH-ir neurons in the VTA on the lesioned side decreased significantly to (34± 2)％.The locomotor activity in 6-OHDA-lesioned rats decreased compared with that in sham-operated rats.Unilaterally lesioning the MFB decreased the percentage of time spent in the center in the open-field test and percentages of open arm entries and open arm time of elevated plus maze test when compared with sham-operated rats.In the sham-operated rats,intra-DG injection of 8-OH-DPAT did not affect anxiety-like behavior.In 6-OHDA-lesioned rats,intra-DG injection of 8-OH-DPAT significantly increased the percentage of time spent in the center at a dose of 100 ng and 500 ng when compared with saline injection into the DG.Injection of WAY-100635 did not affect rats in the two groups.Unilateral 6-OHDA lesions of the MFB in rats significantly decreased DA levels in the ipsilateral striatum,mPFC,amygdale and ventral hippocampus compared with those in sham-operated rats,but had no effect on 5-HT or NA levels in those structures.Conclusion Unilateral 6-OHDA lesion of the MFB not only totally damaged DA neurons in SNc and partly damaged DA neurons in VTA,but also decreased DA level in the ipsilateral striatum,mPFC,amygdale and ventral hippocampus.Unilateral 6-OHDA lesion of the MFB induces anxiety-related behavior,and activation of 5-HT1A receptor in the hippocampal dentate gyrus has anxiolytic effect in the rat model of Parkinson's disease.