Neonatal hippocampal lesion model of schizophrenia in rats: Sex differences and persistence of effects into maturity

Excitotoxic Lesions of the Rat Medial Prefrontal Cortex Effects on Abnormal Behaviors Associated with Neonatal Hippocampal Damage

“…The results of these studies indicate that the neonatally lesioned rats display a constellation of behavioral abnormalities indicative of hyperdopaminergic subcortical activity and hyperresponsivity to glutamate antagonists and that the appearance of these behaviors is delayed until early adult life. Our results and subsequent reports from other laboratories (Flores et al 1996a;Black et al 1996;Wan et al 1996;Wan and Corbett 1997) suggest that this lesion reproduces a constellation of core phenomena associated with schizophrenia, and may thus be used as an animal model of this disorder. Such neonatally lesioned rats also express Received January 5, 1998; revised April 16, 1998; accepted April 30, 1998.…”

“…The results of these studies indicate that the neonatally lesioned rats display a constellation of behavioral abnormalities indicative of hyperdopaminergic subcortical activity and hyperresponsivity to glutamate antagonists and that the appearance of these behaviors is delayed until early adult life. Our results and subsequent reports from other laboratories (Flores et al 1996a;Black et al 1996;Wan et al 1996;Wan and Corbett 1997) suggest that this lesion reproduces a constellation of core phenomena associated with schizophrenia, and may thus be used as an animal model of this disorder. Such neonatally lesioned rats also express behaviors that implicate dysfunction of the PFC (Chambers et al 1996;Sams-Dodd et al 1997), possibly because neonatal damage of the ventral hippocampus disrupts neuronal development of the PFC, with which the hippocampus is closely interconnected (Swanson 1981;Ferino et al 1987;Jay et al 1989;Laroche et al 1990;Jay et al 1992;Carr and Sesack 1996).…”

“…These latter lesions were consistently reported to result in postpubertal emergence of markedly enhanced locomotor responsiveness to stress, amphetamine, and MK-801 Wan et al 1996;Wan and Corbett 1997;Flores et al 1996a;Black et al 1996;Al-Amin et al 1997). So far, the mechanisms of these behavioral alterations have not been identified.…”

Disruption of Latent Inhibition in Rats with Postnatal Hippocampal Lesions

“…It is based on postnatal lesion of the hippocampus of rats induced by infusion of the excitotoxin ibotenic acid, which produced a temporary specific pattern of alterations in a number of dopamine-related behavioral paradigms Weinberger 1995, 1996;Weinberger and Lipska 1995). Comparable results were found by others (Black et al 1996;Flores et al 1996;Wan et al 1996;Wan and Corbett 1997).…”

Caesarean Section Birth Produces Long Term Changes in Dopamine D1 Receptors and in Stress-induced Regulation of D3 and D4 Receptors in the Rat Brain

“…Prenatal stress enhances DA-mediated behavior, increases NAcc D2 receptors and decreases NAcc D3 receptors in adult rats (Henry et al 1995). Neonatal rats receiving ventral hippocampal lesions show enhanced DA-mediated behavior, as adults (Lipska et al 1993;Flores et al 1996a;Black et al 1998;Schroeder et al 1999). Four studies examining DA receptors in this lesion model have reported a slight increase in striatal D1 receptor binding, no change in D2 receptors, and decreased NAcc D3 receptors (Flores et al 1996a), no change in striatal D2 receptor binding (Black et al 1998), no change in Nacc, striatal D1, or D2/3 receptor binding (Lillrank et al 1999), and decreases in striatal D1 and D2 receptor binding (Schroeder et al 1999).…”