Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats

Abstract

The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

Risperidone Pretreatment Prevents Elevated Locomotor Activity Following Neonatal Hippocampal Lesions

“…In agreement with earlier studies (Lipska et al, 1993;Wan et al, 1996;Wan and Corbett, 1997;Weinberger, 1994a, 1995;Flores et al, 1996a, b;Swerdlow et al, 2001;Alquicer et al, 2004), neonatal hippocampal lesions significantly altered locomotor response to novelty and amphetamine in adult rats. We have also identified increased locomotion during the initial 2-h period following change between light and dark cycle in a novel environment as a newly identified behavior altered in adult rats following neonatal hippocampal lesions.…”

Postweaning social isolation enhances morphological changes in the neonatal ventral hippocampal lesion rat model of psychosis

“…The locomotor hyperactivity induced by a novel environment is consistent with an earlier report (Alquicer et al, 2004) that used the same paradigm. It is clear that after weaning, the isolated rats increased locomotor activity in response to a novel environment (Heidbreder et al, 2000;Alquicer et al, 2004).…”

“…The combination of both conditions (nVH-lesion plus social isolation) resulted in greater decreases in dendritic length of PFC and NAcc neurons while increases in dendritic spine density of the medium spiny neurons were seen in the NAcc. Moreover, these morphological changes are associated with increased locomotor activity in a mildly stressful novel environment, a behavioral abnormality often described in socially isolated and nVH-lesioned rats (Jones et al, 1992;Flores et al, 1996Flores et al, , 2005Heidbreder et al, 2000;Silva-Gomez et al, 2003a;Alquicer et al, 2004).…”

“…It is clear that after weaning, the isolated rats increased locomotor activity in response to a novel environment (Heidbreder et al, 2000;Alquicer et al, 2004). The nVH-lesion also induced increased locomotor activities in response to a novel environment, stress or amphetamine (Lipska et al, 1993;Flores et al, 1996;Brake et al, 1999).…”

“…It emerges at about PD18, peaks during PD28-PD35 and decreases with age until sexual maturity (Baenninger, 1967;Meaney and Stewart, 1979;Thor and Holloway, 1984;Vanderschuren et al, 1997). Social isolation in rats produces a well characterized syndrome consisting of hyperactivity (Jones et al, 1992;Hall et al, 1998), increased locomotor activity in response to a novel environment and dopaminergic (DA) agonists (Jones et al, 1992;Hall et al, 1998;Alquicer et al, 2004), decreased pain threshold (PuglisiAllegra and Oliverio, 1983), deficit in prepulse inhibition (Geyer et al, 1993;Varty and Higgins, 1994;Wilkinson et al, 1994;Domeney and Feldon, 1998;Weiss et al, 1999) and altered responses to neuroleptic drugs (Sahakian and Robbins, 1977). These behavioral effects involve various pathways, in particular, the DA mesolimbic system (Jones et al, 1992;Geyer et al, 1993;Hall et al, 1998;Weiss et al, 1999).…”