THE ROLE OF D1 RECEPTORS AND D2 RECEPTORS IN THE HEIGHTENED LOCOMOTION INDUCED BY DIRECT AND INDIRECT DOPAMINE AGONISTS IN RATS WITH HIPPOCAMPAL DAMAGE - AN ANIMAL ANALOG OF SCHIZOPHRENIA

Rats with limbic system damage display increases in responsivity to se nsory stimulation and changes in the sensitivity to amphetamine, sugge sting that their condition may parallel that of human schizophrenia. T his experiment examined locomotion and stereotyped behavior in mature, male rats that had received aspirative lesions of the hippocampus, co ntrol lesions of the overlying parietal cortex, or were unoperated con trols. Locomotion, measured as photocell beam breaks, was recorded dur ing 2- or 3-h test sessions. Behavioral stereotypy was simultaneously rated. Hippocampal lesioned rats exhibited a selective enhancement in locomotion following D-amphetamine (0.0-5.6 mg/kg) when compared to an imals in the control groups. Similar results were observed following i njections of apomorphine (0.0-0.25 mg/kg), a mixed D 1 and D2 agonist. In order to determine if Dl or D2 receptors were involved in this inc reased locomotion, the Dl agonist SKF 38393 (0.0-15 mg/kg) and the D2 agonist quinpirole (0.0-0.5 mg/kg) were tested alone and in combinatio n. Hippocampal-ablated rats showed significantly increased locomotion only in response to quinpirole, suggesting that these lesion-induced i ncreases were largely mediated by D2 receptors. When both drugs were a dministered together, SKF 38393 further enhanced the locomotor stimula ting effects of quinpirole in hippocampal lesioned rats, indicating a synergistic interaction between D1 and D2 receptors in the modulation of locomotion. These findings provide further evidence of hippocampal modulation of locomotion and suggest that dopaminergic mechanisms in t he nucleus accumbens, probably involving changes in receptor sensitivi ty, are involved. The results are discussed in relation to the functio nal roles of the nucleus accumbens and in terms of their implications for mental diseases including schizophrenia.