Heterogeneity of the hippocampus: effects of subfield lesions on locomotion elicited by dopaminergic agonists

Abstract Structural abnormalities in the hippocampal formation and overactive dopamine neurotransmission in the ventral striatum are thought to be key pathologies in schizophrenia. This experiment examined the functional contribution of different hippocampal subfields to locomotion elicited by d-amphetamine (0.32-3.2 mg/kg) and the direct agonists quinpirole (0.02-0.5 mg/kg) and SKF 38393 (2.5-15.0 mg/kg). Male rats served as unoperated controls or received one of six different lesions (hippocampal formation, fimbria-fornix, subiculum, CA3-4, entorhinal cortex or dentate gyrus (DG)). The main results indicated that extensive ibotenic acid-induced lesions of the hippocampal formation, or colchicine-induced lesions of the DG enhanced locomotion elicited by the D2 agonist quinpirole. Electrolytic lesions of the fimbria-fornix, in comparison, had much larger effects and resulted in increases in the locomotor response to amphetamine and quinpirole. These results extend previous demonstrations of hippocampal modulation of the ventral striatum by showing that this modulatory influence is dependent on both the location and total extent of cell loss within the hippocampal formation. The results are discussed in relation to the causes of and neurophysiological mechanisms involved in enhanced drug-induced locomotion and in terms of their implications for mental diseases including schizophrenia.