Biochemical Analysis of Cerebrospinal Fluid Changes in Response to Drug Administration.
Abstract
We have successfully designed and tested a chronic, remote sampling system for CSF with a total dead space of less than 0.06 ml. A monkey model has been developed for the study of drug abuse while monitoring behavior, CSF neurochemical changes and cardiovascular effects of selected drugs. The first series of drug studies has been completed using the d- and l-stereoisomers of amphetamine. Both isomers at levels of 1.5 mg-kg effect the norepinephrine neuronal system as evidence by the pronounced peripheral respiratory and cardiovascular effects. However at this same dosage level the d- isomer results in striking behavioral changes associated with dopaminergic neurons. The l- isomer does not produce any stereotyped behavior and only creates general conditions of restlessness. We found that levels of the serotonin metabolite 5-HIAA in the CSF were essentially unchanged by either amphetamine isomer although there was a greater tendency to decrease after the d- isomer than the l- isomer. CSF levels of a dopamine metabolite HVA decreased significantly after the d- isomer indicating possible increased rates of release of dopamine, reduced reuptake of dopamine and increased possible o-methylation to 3-methoxy dopamine. These changes in HVA with the d-isomer are supported by the simultaneous tendency for CSF levels of 5-HIAA to decrease and support the hypothesis of MAO inhibition. Levels of HVA in the CSF were essentially unaffected by the l-amphetamine isomer at the same dosage levels. We observed significant changes in peripheral cardiovascular and respiratory systems which would be associated with norepinephrine neurons and which were produced by both amphetamine isomers with nearly equal effectiveness.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 11, 1973
- Accession Number
- ADA096753
Entities
People
- Barry Burns
- Joseph V. Brady
Organizations
- Johns Hopkins University