Isolation rearing in the rat disrupts the hippocampal response to stress

Abstract

AbstractöBoth human schizophrenia and the e¡ects of isolation rearing in rats produce de¢cits in hippocampal and cortical functioning. This study was concerned with identifying changes associated with altered neuronal function in the rat hippocampus following isolation rearing. Rats were isolated from weaning at 21 days postnatal for 6 weeks and the hippocampal sensitivity to isolation rearing and stress were studied using c-fos immunohistochemistry and in vivo microdialysis. Isolation rearing altered neuronal activity measured by Fos-like immunoreactivity in the speci¢c brain areas as measured by either increased or reduced expression. Basal neuronal activity in the ventral CA1 hippocampus in isolationreared rats was notably higher compared to group-reared rats but markedly lower Fos-like immunoreactivity was found in the central and basolateral nuclei of the amygdala. Exposure to stress produced di¡erential e¡ects on neuronal activity in isolation-reared rats between the dorsal and ventral hippocampus, with increased Fos-like immunoreactivity in the dorsal hippocampus but lower Fos-like immunoreactivity in the ventral hippocampus compared to group-reared rats. These results indicate that isolation rearing may alter the relationship between hippocampal neuronal function in the dorsal and ventral hippocampus. An in vivo microdialysis study showed that systemically administered parachloroamphetamine (2.5 mg/kg, i.p.) enhanced extracellular 5-hydroxytryptamine (5-HT) in the dorsal hippocampus in groupreared but not in isolation-reared rats. Restraint stress had no e¡ect on hippocampal extracellular 5-HT in group-reared rats but reduced levels in isolation-reared rats during the period of restraint. Inescapable mild footshock produced a marked increase in extracellular hippocampal 5-HT in group-reared but not isolation-reared rats.Overall the results provide extensive evidence that isolation rearing alters presynaptic 5-HT hippocampal function and that the neuronal response to stress is altered by isolation. Isolation rearing in the rat alters hippocampal function, including the serotonergic system, leading to changes in neurotransmitter systems in other brain areas. These changes may model aspects of human neurodevelopmental disorders such as schizophrenia. ß

The Serotonergic Projection from the Median Raphe Nucleus to the Ventral Hippocampus is Involved in the Retrieval of Fear Memory Through the Corticotropin-Releasing Factor Type 2 Receptor

“…Although dopamine receptors in the ventral hippocampus are involved in working memory and complex learning (Wilkerson and Levin, 1999;Umegaki et al, 2001), they may not be involved in fear memory retrieval. Moreover, preliminary data showed that the serotonin release in the dorsal hippocampus was not altered by exposure to footshock box (Supplementary Figure S5), although serotonin release in the dorsal hippocampus would be involved in stress responses other than fear memory retrieval (Matsuo et al, 1996;Muchimapura et al, 2002). These data also support our conclusion that the serotonergic projection from the MRN to the ventral hippocampus is selectively involved in the retrieval of fear memory through the CRF 2 receptor in the MRN.…”

Early maternal deprivation induces gender‐dependent changes on the expression of hippocampal CB1 and CB2 cannabinoid receptors of neonatal rats

“…Similar to the MD model, isolation rearing produces a number of postpubertal behavioral and neurochemical changes, some of which are similar to those observed in psychoses, in particular, a disruption in prepulse inhibition which is indicative of deficits in sensorimotor gating (Geyer et al, 1993;Cilia et al, 2005). Isolation rearing in rats has also been shown to alter hippocampal function, including the serotonergic system (Muchimapura et al, 2002(Muchimapura et al, , 2003. Moreover, raising rats in isolation led to a significant decrease in CB 1 receptor expression in the caudate putamen and the amygdale, as well as a significant increase in FAAH expression in the caudate putamen and the nucleus accumbens core and shell (Malone et al, 2008).…”

Isolation-Induced Changes in Ultrasonic Vocalization, Fear-Potentiated Startle and Prepulse Inhibition in Rats

“…These fi ndings have been replicated in a recent work in our laboratory, in which we used rats isolated immediately after weaning (21 days postnatal) for 10 weeks continuously, housed in the same room with rats reared under normal social conditions [35] . The reason that has been given for these effects seems to be related to the lack of essential sensory information and input from appropriate social contact, olfactory information and environmental stimuli for the normal development of brain structure and neurotransmitter function, resulting in altered behavior in adult life compared to group-reared rats [24,46] .…”