Effects of anesthetics and electrical stimulation on nigrostriatal dopaminergic neurons

Induction of anesthesia with pentobarbital (40 mg/kg), urethane (1.8 g/kg), chloral hydrate (400 mg/kg) or ketamine (150 mg/kg) followed by a 20-min sham implantation of a bipolar electrode in substantia nigra fibers caused a marked, ipsilateral increase in caudate dihydroxyphenylacetic acid (DO-PAC). Conversely, no sham stimulation was found after gamma-butyrolactone (500 mg/kg) anesthesia or in a paralyzed, artificially respired preparation. By using gamma-butyrolactone anesthesia, the nigrostriatal fibers were electrically stimulated (25 Hz, 1.5 msec duration) at differing current intensities (40, 80, 100, 120 and 180 microA). The maximum increase in caudate DOPAC occurred at 120 microA. Electrical stimulation (100 microA, 25 Hz, 1.5 msec duration) in the paralyzed preparation yielded similar increases in caudate DOPAC. By using a 50% effective current (100 microA), variation of the frequency (5, 10, 25 and 125 Hz) produced a maximum in caudate DOPAC at 10 Hz. These data reveal an interaction between many anesthetics and physical disruption of dopaminergic neurons, as well as provide an in vivo model of stimulus-dependent dopamine release.