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 with several neurological and psychiatric diseases which may have a viral aetiology. The effect of Semliki Forest virus (SFV) on 5-hydroxytryptamine (5-HT1A and 5-HT2A) receptors in mouse brain has been assessed by membrane homogenate binding and autoradiography. Adult mice were injected with saline or virus and brains removed 2, 6, 14, 22 and 35 days after infection. 5-HT1A and 5-HT2A receptors were characterised by saturation studies using [3H] 8-OH-DPAT and [3H] Ketanserin respectively. SFV infection increased 5-HT1A receptor numbers by up to 80% in the cortex on days 6, 14, and 22 but had no effect on Bmax in the midbrain, pons/medulla and the hypothalamus. SFV infection did not affect 5-HT2A receptor number in any of the brain regions studied and the affinity (Kd) of either ligand for 5-HT1A or 5-HT2A receptors was unaffected. Autoradiographic mapping of 5-HT1A receptors in SFV-infected brain showed substantially higher binding in nucleus accumbens, tenia tecta, septohippocampal nucleus, septum, medial and basolateral amygdaloid nucleus, anterioventral preoptic nucleus, hippocampus, interpeduncular nucleus, frontal, lateral orbital, and entorhinal cortex and claustrum on days 6 and 14. Elevated binding persisted in tenia tecta, frontal, lateral orbital, entorhinal cortex, and hippocampal formation to day 22. Autoradiography of 5-HT2A receptors using [3H] 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 results show SFV infection induces a regionally selective upregulation of 5-HT1A but not 5-HT2A receptors.