Willis G L, Sleeman M, Pavey G M, Smith G C
Brain Res. 1987 Feb 10;403(1):15-21. doi: 10.1016/0006-8993(87)90117-x.
Despite the large volume of literature during the past 15 years addressing the problem concerning the neurochemical specificity of 6-hydroxydopamine (6-OHDA), there is still disagreement over this issue. While some claim that the catecholamine-specific effects of this drug can be maximized by controlling the dose injected, others claim that all doses of 6-OHDA produce non-specific damage (NSD), thereby contraindicating its use in experimental paradigms. In the present study, we examined the degree of neurochemical specificity of 6-OHDA by comparing the volume of proximal accumulation to that of NSD, produced by 6-OHDA (2 microliter of 8 micrograms/microliter) or radiofrequency (RF) lesions (60 degrees C for 50 s and 45 degrees C for 30 s), placed in the medial forebrain bundle. The volume of NSD and accumulation produced by 6-OHDA was significantly less than that produced by large RF lesions which had a similar effect on the gross behaviour of albino rats. Smaller RF lesions produced similar volumes of NSD but less amine accumulation than did 6-OHDA, and did so without affecting normal behaviour. The ratio of NSD to accumulation in 6-OHDA treated rats was 3/1, while large and small RF lesions produced a NSD/accumulation ratio of 15/1. The present study introduces a novel method of determining the degree of neurochemical specificity which can be achieved with 6-OHDA and reveals that it is several magnitudes more neurochemically specific than RF lesions.