The amine accumulation-producing capacity of 6-hydroxydopamine and its neurochemical specificity

There was considerable research during the 1970's addressing the problem of the neurospecificity of 6-hydroxydopamine (6-OHDA). Despite the numerous attempts to define the criteria governing the use of this drug in experimental paradigms, some believed that specific damage to catecholamine (CA)-containing neurones could be achieved only by controlling the dose injected, while others claimed that the neurotoxic effect that this drug had on non-CA systems was so severe that it contraindicated its use experimentally. The issue still remains unresolved. In the present study, we examined the degree of neurochemical specificity produced by 6-OHDA or radiofrequency (RF) lesions by comparing the quantity of amine accumulation to the amount of physical damage at the lesion site (termed non-specific damage, NSD) which each technique produced. The volume of NSD produced by 6-OHDA (2 microliter of 8 micrograms/ul) was significantly less than that produced by large RF lesions (60 degrees C for 50 sec) both of which has a similar effect on the regulation of short term body weight. Both types of lesions produced similar quantities of amine accumulation. Smaller RF lesions (45 degrees C for 30 sec) produced the same amount of NSD as did 6-OHDA but significantly less amine accumulation and had no effect on body weight regulation. The ratio of NSD to amine 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 results reveal that the neurochemical specificity of 6-OHDA is several magnitudes greater than with RF lesions, when using the criteria as defined in the present experiment.(ABSTRACT TRUNCATED AT 250 WORDS)