Neurotoxicity induced by the D-1 agonist SKF 38393 following microinjection into rat brain

Microinjection of the D-1 agonist R-SKF 38393 into rat striatum resulted in extensive neurotoxic damage as revealed by the presence of large lesions upon histological analysis. These lesions were observed following a single injection of the drug into the ventrolateral striatum (30 micrograms/0.5 microliters) or nucleus accumbens (3.0 or 30 micrograms/0.5 microliters). This neurotoxic damage was also observed following microinjection of the inactive isomer S-SKF 38393. The mechanisms underlying these effects are presently unknown. The use of this compound for intracerebral microinjection studies should be re-evaluated. In view of the usefulness of central microinjections in studying the role of D-1 and D-2 receptors in behavior, it is suggested that alternative D-1 agonists, or ways of minimizing the toxicity of SKF 38393, should be considered.