Electrical self-stimulation of the brain: a model for the behavioral evaluation of toxic agents.

Rats implanted chronically with electrodes in the posterior lateral hypothalamus were trained to press levers in order to stimulate the brain electrically. Brief exposures to low oxygen concentrations reduced the lever pressing rate proportionately with the reduction in inspired oxygen. Similar reductions in self-stimulation rates could be observed in animals exposed to carbon monoxide or the organic solvent, trichloroethylene. Prolonged exposures of animals to hypoxia in chambers where self-stimulation rates as well as food and water intake via lever pressing were monitored, indicated that as oxygen concentration declined self-stimulation rates showed a marked increase for 12 hr followed by a decline. Food and water intake were depressed. This increase in self-stimulation was only observed at low (20 degrees C) ambient temperatures and was accompanied by central depletion of norepinephine. At high (30 degrees C) ambient temperatures, self-stimulation was depressed by hypoxia. The data show the importance of comparing acute with chronic exposure to toxic agents, as well as the influence of environmental temperature in influencing behavioral events. In addition, the data indicate that the self-stimulation technique offers unique advantages over behavior maintained by food or water reinforcers in evaluating toxic compounds.