Neonatal Ventral Hippocampal Lesions Potentiate Amphetamine-Induced Increments in Dopamine Efflux in the Core, but Not the Shell, of the Nucleus Accumbens

Background In rats, neonatal ventral hippocampal lesions (NVHLs) result in the postpubertal emergence of alterations reminiscent of several features of schizophrenia, including increased responsivity to the behavioral effects of amphetamine (AMPH). The precise nature of presynaptic aspects of accumbal dopamine (DA) function in these alterations is however uncertain: previous studies have found that the exacerbated responses to AMPH of NVHL rats are associated with either decreased or unchanged DA efflux in the nucleus accumbens (NAc) as compared with shams. Because these studies investigated DA output in the whole NAc, it was considered of interest to examine the impact of NVHLs on DA transmission in NAc subregions involved in distinct aspects of goal-directed behavior. Methods The effects of AMPH (.25 mg/kg, subcutaneous) on the accumbal DA efflux of adult rats were evaluated using brain microdialysis, and motor activity was recorded alongside dialysate sample collection. Results The enhanced behavioral responsivity to AMPH of NVHL rats is associated with potentiation of AMPH-induced DA output in the NAc core and a concomitant attenuation of DA overflow in the NAc shell. Conclusions The functional alterations in the NAc core induced by NVHLs provide a link between the hippocampal damage and striatal DA hyperactivity in schizophrenia