Intracerebroventricular vs. subcutaneous drug administration: apples and oranges?

For numerous reasons, the icv route is commonly used to administer endogenous opioid peptides and other newly discovered or synthesized substances and may often indicate whether the drug has actions on the brain. Effects are then routinely compared to the actions of prototypic agents given by some systemic route, such as sc or ip. Unfortunately, there is little appreciation that qualitative as well as quantitative differences can be seen when the same drug is administered by central as opposed to peripheral routes. Numerous factors undoubtedly contribute to the final effect. Whatever the explanation, failure to recognize that such differences may occur could result in incorrect conclusions as to the involvement of specific receptor types or subtypes.