Effects of ibotenic acid lesion of the medial prefrontal cortex on dopamine agonist-related behaviors in the rat

Behavioral responses to apomorphine and to the selective D₁ and D₂ dopamine receptor agonists SK&F38393 and quipirole were evaluated in rats following ibotenic acid (IA) or sham lesion of the medial prefrontal cortex (MPFC). IA-lesioned rats showed an increased responsiveness to the postsynaptic effects of all of the dopamine agonists. Patterns of the responses to the selective agonists administered alone and in combination suggest that these effects might be due to selective increases in the sensitivity of postsynaptic D₁ receptor-associated mechanisms. In addition, IA-lesioned rats pretreated with saline were hyperactive in comparison to sham-lesioned rats when animals were exposed to a novel open field, but spontaneous motor activity did not differ between these two groups when animals were pretreated with low doses (0.03 mg/kg) of quinpirole. The fact that hyperactivity observed in lesioned animals is inhibited by a dose of quinpirole that is felt to act presynaptically, selectively attenuating endegenous dopaminergic tone, suggests that effects of the MPFC lesion may be mediated presynaptically as well.