Regional changes in 5-HT1A but not in 5-HT2A receptors in mouse brain after Semliki Forest virus infection: radioligand binding and autoradiographic studies

Dysfunction of brain 5-hydroxytryptaminergic systems has been associated wi th several neurological and psychiatric diseases which may have a viral aet iology. The effect of Semliki Forest virus (SFV) on 5-hydroxytryptamine (5- HT1A and 5-HT2A) , receptors in mouse brain has been assessed by membrane h omogenate binding and autoradiography. Adult mice were injected with saline or virus and brains removed 2, 6, 14, 22 and 35 days after infection. 5-HT 1A and 5-HT2A receptors were characterised by saturation studies using [H-3 ] 8-OH-DPAT and [H-3] Ketanserin respectively. SFV infection increased 5-HT 1A receptor numbers by up to 80% in the cortex on days 6, 14, and 22 but ha d no effect on B-max in the midbrain, pons/medulla and the hypothalamus. SF V infection did not affect 5-HT2A receptor number in any of the brain regio ns studied and the affinity (Kd) Of either ligand far 5-HT1A or 5-HT2A rece ptors was unaffected. Autoradiographic mapping of 5-HT1A receptors in SFV-i nfected brain showed substantially higher binding in nucleus accumbens, ten ia tecta, septohippocampal nucleus, septum, medial and basolateral amygdalo id nucleus, anterioventral preoptic nucleus, hippocampus, interpeduncular n ucleus, frontal, lateral orbital, and entorhinal cortex and claustrum on da ys 6 and 14. Elevated binding persisted in tenia tecta, frontal, lateral or bital, entorhinal cortex, and hippocampal formation to day 22. Autoradiogra phy of 5-HT2A receptors using [H-3] Ketanserin showed no difference in the binding in SFV-infected brains. A decrease in plasma corticosterone levels in SFV-infected mice was observed on post infection days 6 and 22. These re sults show SFV infection induces a regionally selective upregulation of 5-H T1A but not 5-HT2A receptors.