Intracranial injection of drugs: Comparison of diffusion of 6-OHDA and guanethidine

• Published in: Pharmacology, biochemistry and behavior Vol. 3; no. 2; pp. 205 - 217
• Main Authors: Evans, Barbara K., Armstrong, S., Singer, G., Cook, R.D., Burnstock, G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.1975
• Subjects: 6-OHDA; Amygdala - drug effects; Amygdala - metabolism; Animals; Brain Chemistry - drug effects; Catecholamine-depletion; Catecholamines - analysis; Diffusion; Drug diffusion; Guanethidine; Guanethidine - administration & dosage; Guanethidine - metabolism; Guanethidine - pharmacology; Histocytochemistry; Hydroxydopamines - administration & dosage; Hydroxydopamines - metabolism; Hydroxydopamines - pharmacology; Hypothalamus - drug effects; Hypothalamus - metabolism; Injections; Intracranial injection; Male; Microscopy, Electron; Microscopy, Fluorescence; Nerve Degeneration - drug effects; Rats; Stereotaxic Techniques - adverse effects; Substantia Nigra - drug effects; Substantia Nigra - metabolism; 6-OHDA; Guanethidine; Drug diffusion; Intracranial injection; Catecholamine-depletion
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(75)90150-1

Marked differences in extent of diffusion have been shown with the fluorescence histochemical method between guanethidine and 6-OHDA (64 μg in 2 μl) when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage up to 1 mm in diameter and attributed to the implantation of cannulae and placebo injection was observed. A further area of generalized damage occurred following the injection of drugs and was far greater for 6-OHDA (2 mm) than for guanethidine (0.3 mm). Guanethidine, but not 6-OHDA, caused specific damage to catecholamine-containing neurons up to a distance of at least 3 mm and more from the cannula tip. These striking differences between the effects of intracranial injection of 6-OHDA and guanethidine are discussed in terms of the uptake and degradation of the two drugs and the anatomical features of the injection site; they are not explicable in terms of experimental conditions such as concentration, volume of injection, molecular weight or lipid solubility. The different patterns of damage would not easily be distinguished by biochemical analyses and the catecholamine specificity of 6-OHDA in studies of the central nervous system must be seriously questioned. Vascularization of chronically implanted cannula tracks and the presence of anatomical diffusion barriers are also discussed in relation to the diffusion of drugs injected intracranially.