Alterations in neurotransmitter receptors and glucose use after unilateral orbital enucleation

Abstract

Serotonin (5-hydroxytryptamine; 5-HT), acetylcholine and γ-aminobutyric acid (GABA) are neurotransmitters in the rat visual system. Using quantitative autoradiography, the effect of unilateral orbitral enucleationon [ 3H]5-HT, [ 3H]ketanserin, [ 3H]quinuclidinyl benilate (QNB) and [ 3H]muscimol binding to 5-HT 1, 5-HT 2, muscarinic and GABA A receptors has been examined within anatomical components of the visual pathway at 4 time points up to 20 days after the lesion. The functional deficit was assessed in the same animals using quantitative [ 14C]2-deoxyglucose autoradiography. At 1 day after unilateral orbital enucleation, there were no significant alterations in ligand binding although local cerebral glucose use was reduced in primary visual structures in the visually deprived hemisphere. At 5 days post-enucleation, however, [ 3H]5-HT binding was significantly reduced in both the visually deprived superior colliculus (by 17%) and dorsal lateral geniculate body (DLG) (by 33%). There were similar alterations in the binding of this ligand in these primary retinal projections areas at 10 and 20 days after orbital enucleation, but there were no changes in secondary areas (e.g. visual cortex) at any time point. [ 3H]Muscimol binding was significantly reduced in the visually deprived DLG (30%) and visual cortex (21%) only at 20 days post-lesion, whilst [ 3H]ketanserin and [ 3H]QNB were not altered in any region in the visually deprived hemisphere at any time point post-enucleation. At 10 and 20 days post-enucleation, the degree of [ 3H]5-HT, and [ 3H]muscimol binding deficits in visually deprived structures correlated significantly with the level of reduced metabolic activity in these areas ( r = 0.700andr = 0.543respectively). The specificity and regional and temporal heterogeneity of neurotransmitter receptor binding alterations provides evidence of selective adjustments within visual system component6s in response to orbital enucleation.