Supersensitivity of the noradrenergic system in the spinal cord following intracisternal injection of 6-hydroxydopamine.
The intracisternal administration of 6-hydroxydopamine (6-OHDA; 100 micrograms on two consecutive days) resulted in a 90-95% depletion of norepinephrine (NE) in the spinal cord 3-60 days following administration of the drug. At 90 days following injection of 6-OHDA, the depletion was only 60% suggesting the regrowth of NE-containing fibers. Consistent with the depletion of NE, 3-60 days after the injection of 6-OHDA a 50-80% decrease in the uptake NE occurred with only a 25% decrease 90 days after administration of 6-OHDA. Associated with decreases in NE and its uptake was a 100-200% increase in the accumulation of NE-stimulated cyclic AMP in slices of spinal cord tissue from 6-OHDA-treated rats. The increased response was evident at 3-60 days after injection of 6-OHDA decreasing on day 90 to 40% above control. No shift in the EC50 for NE was evident and the specificity of agonists for this response was limited to agents with alpha and/or beta-adrenergic receptor activation properties. Radioligand receptor binding techniques, utilizing [3H]prazosin for alpha1 receptors and [3H]dihydroalprenolol for beta receptors demonstrated that increases in the Bmax of response of alpha1 (30-50%) and beta (15-20%) receptors in spinal cord may mediate the enhanced response of NE-stimulated cyclic AMP following the administration of 6-OHDA. This is indicated by similar time-dependent patterns of onset and termination of increased receptor binding and the accumulation of NE-stimulated cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002946:Cisterna Magna; D000242:Cyclic AMP / Q000378:metabolism*; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D016627:Oxidopamine; D000242:Cyclic AMP; D009638:Norepinephrine