ABSTRACT
Covalently bonding multiple fluorine atom tags to the precursors of monoamines could provide compounds for functional imaging. Theoretically, the fluorine atoms can produce detectible signal if concentrated in vesicles inside neurons. Prior to committing more costly resources to the project, evidence was sought for uptake of the molecules into neurons in living organisms. Two 19F tag configurations of seven or nine atoms were investigated. Crayfish aggression provided a paradigm for obtaining preliminary data on the scarce new molecules. After establishing that 5-hydroxytryptophan (5-HTP) elicited serotonin-like effects, the fluorine tagged versions (PF-5-HTP) were investigated; then, the elevated aggression produced by these precursors to serotonin was blocked by coadministering fluoxetine. Treatment order effects and interrater reliability of the behavioral inventory were evaluated. Preliminary evidence that these imaging compounds are taken up into neurons obtained by studying crayfish behavior later found support using more sophisticated neuroscience techniques.
Subject(s)
Aggression/physiology , Astacoidea/physiology , Fluorine/physiology , Aggression/drug effects , Animals , Astacoidea/drug effects , Behavior, Animal/drug effects , Behavior, Animal/physiology , Dominance-Subordination , Fluoxetine/pharmacology , Halogenation/physiology , Neurons/drug effects , Neurons/physiology , Serotonin/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacologyABSTRACT
PURPOSE: To create a probe for investigating neural development in chicks using magnetic resonance, a C(3)F(7) tag was bonded to the indole ring of 5-hydroxytryptophan (5-HTP). Immunoassays indicate that a low dose (5 microg/egg) administered in ova results in 0.5-1.0 microg accumulating in a 250 microL midbrain. PROCEDURES: Given the potential for developmental neurotoxicity of a compound that replaces an endogenous neurotransmitter, we investigated the effects of acute exposure during development. RESULTS: No qualitative differences were observed between treatment groups. Differences in mortality rates between treatment groups were not statistically significant [X(2)(obs)=2.30, X(2)(crit) (df=2)=5.99, P>.05]. CONCLUSION: The no-effect dose for in ova administration of C(3)F(7) tagged5-HTP is 5 microg/egg on Day 17.
Subject(s)
Fluorocarbons/toxicity , Nervous System/embryology , Serotonin/analogs & derivatives , 5-Hydroxytryptophan/toxicity , Animals , Chickens , Fluorine , Fluorocarbons/chemistry , Magnetic Resonance Imaging , Nervous System/drug effects , Ovum/drug effects , Serotonin/chemistry , Serotonin/toxicity , Serotonin Antagonists/toxicityABSTRACT
A new tool for magnetic resonance, L-6-heptafluorobutyryl-5-hydroxytryptophan, was synthesized and investigated using an antibody to perfluoroalkyl moieties developed previously. To be useful as an imaging agent, the compound must cross the blood brain barrier and then be concentrated in vesicles in serotonergic neurons in order to accumulate in sufficient quantity for in vivo detection to be possible. The novel imaging compound was administered in ova to domestic chicks (Gallus domestics) to investigate the bioavailability and uptake dynamics of the compound in this model organism. Typical immunoassay methods were ineffective, so a new technique was developed which binds amines and amino acids to the walls of acid-functionalized cuvettes. The first study established the presence of higher quantities of the tags in neural and liver tissue than in heart tissue. A second study investigated regional differences, with the midbrain containing more tagged compounds than the frontal lobe sample, and the frontal lobe sample containing more than the occipital or cerebellum samples. These studies demonstrate that the compound follows the pathway of endogenous serotonin. A third study investigated uptake dynamics of the novel compound. Maximum concentration of the tagged molecule in the brain was achieved three days after injecting Incubation Day 14 eggs, suggesting that it bioaccumulates in vivo. This new immunoassay technique used to detect the novel compound in tissue samples demonstrated good repeatability.
