6-hydroxydopamine lesioning of dopamine neurons in neonatal and adult rats induces age-dependent consequences

Abstract

Over 45 years ago, it was discovered that the compound 6-hydroxydopamine (6-OHDA) destroys catecholamine (CA)-containing neurons when injected directly into the brain. Refinements in the use of 6-OHDA led to the development of dopamine (DA)-denervated rats to model Parkinson's disease (PD) and Lesch-Nyhan syndrome (LNS), in which loss of DA-containing neurons is a prominent feature. Differing functional characteristics were eventually discovered in DA-denervated rats depending on the age at which the DA was reduced. With 6-OHDA lesioning of CA neural systems in the brain, key discoveries were made regarding how these systems control specific physiological functions and behavioral responses. Important neurobiological concepts emerged as well, including receptor supersensitivity, Dj/D2-DA receptor interaction, and Dj-DA priming of supersensitivity, including neural mechanisms likely relevant to clinical symptoms modeled by the 6-OHDA treatment. In this chapter, behavioral, neurochemical, structural, and pharmacological studies carried out in adult and neonatal 6-OHDA-treated rats are reviewed, and findings are compared and contrasted. To date, age-dependent lesioning of DA neurons in rats with 6-OHDA continues to play an important role in the development and validation of new therapies for clinical disorders with brain DA reduced.