Sensitization to cocaine's motor activating properties produced by electrical kindling of the medial prefrontal cortex but not of the hippocampus

Abstract

A substantial body of evidence has accumulated that implicates NMDA systems in the neural changes that are associated with the development of both electrical kindling of limbic sites and sensitization to the behavioral effects of repeated stimulant exposure. This study sought to establish whether electrical kindling of the brain was a sufficient condition for inducing sensitization to cocaine's motor activating effects and, if so, whether the cross sensitization was a result of kindling of a specific locus. Rats received daily electrical stimulation of either the medial prefrontal cortex or the hippocampus. Other rats received the electrode implants and were handled daily but received no electrical stimulation. Stage 5 seizures developed in response to the stimulation in 32–35 days. Once this criterion of kindling was established and following a 14 day waiting period the effectiveness of cocaine (0.0, 5.0 or 10.0 mg/kg) in elevating horizontal motor activity was determined. For all 3 groups (sham controls, prefrontal cortical and hippocampal stimulated rats) cocaine produced a dose-dependent increase in horizontal activity. The slam controls and hippocampal rats did not differ in the magnitude of the cocaine-produced effect. However, rats that had received stimulation of the prefrontal cortex showed heightened levels of cocaine-induced activity that were particularly apparent in response to 10.0 mg/kg cocaine. These data suggest that kindling of the prefrontal cortex had sensitized rats to the behavioral effects of cocaine. Since the NMDA system has been implicated in both electrical kindling and sensitization produced by repeated stimulant exposures it is possible that the development of behavioral sensitization is a result of increased sensitivity of specific glutamatergic inputs that arise from a prefrontal cortical substrate and project to cocaine-sensitive sites.