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  • 2000-2004  (3)
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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Excitotoxic neonatal ventral hippocampus (NVH) lesions in rats result in characteristic post-pubertal hyper-responsiveness to stress and cognitive abnormalities analogous to those described in schizophrenia and suggestive of alterations in dopamine (DA) neurotransmission. Converging lines of evidence also point to dysfunctions in the cortical cholinergic system in neuropsychiatric disorders. In previous studies, we observed alterations in dopaminergic modulation of acetylcholine (Ach) release in the prefrontal cortex (PFC) in post-pubertal NVH-lesioned rats. These two neurotransmitter systems are involved in the stress response as PFC release of DA and Ach is enhanced in response to some stressful stimuli. As adult NVH-lesioned rats are behaviorally more reactive to stress, we investigated the effects of NVH lesions on tail-pinch stress-induced Ach and DA release in the PFC. Using in vivo microdialysis, we observed that tail-pinch stress resulted in significantly greater increases in prefrontal cortical Ach release in post-pubertal NVH-lesioned rats (220% baseline) compared with sham-operated controls (135% baseline). Systemic administration of the D1-like receptor antagonist SCH 23390 (0.5 mg/kg i.p.) or the D2-like receptor antagonist haloperidol (0.2 mg/kg i.p.), as well as intra-PFC administration of the D2-like antagonist sulpiride (100 µm), reduced stress-induced Ach release in PFC of adult NVH-lesioned rats. By contrast, intra-PFC administration of SCH 23390 (100 µm) failed to affect stress-induced Ach release in PFC of NVH-lesioned rats. Interestingly, using in vivo voltammetry, stress-induced stimulation of PFC DA release was found to be attenuated in adult NVH-lesioned rats. Taken together, these data suggest developmentally specific reorganization of prefrontal cortical cholinergic innervation notably regarding its regulation by DA neurotransmission.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Excitotoxic lesion of the ventral hippocampus in neonatal rats is a putative animal model of schizophrenia with characteristic developmental abnormalities in dopaminergic neurotransmission and prefrontal cortical functions. Converging evidence also points to the involvement of the central cholinergic system in neuropsychiatric disorders. These two neurotransmitter systems are interlinked in the prefrontal cortex (PFC) where dopamine stimulates acetylcholine (ACh) release. In the present study, we investigated the role of dopamine in the developmental regulation of prefrontal cortical ACh release and the expression of nicotinic and muscarinic receptors in pre- and post-pubertal rats with neonatal ibotenic acid-induced lesions of the ventral hippocampus (NVH). In vivo microdialysis in the PFC revealed that systemic injections of the D1-like receptor agonist (±)-6-chloro-7,8-dihydroxy-1-phenyl2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) (2.5 and 5.0 mg/kg i.p.) caused significantly higher ACh release in post-pubertal NVH-lesioned animals (250 and 300% baseline for 2.5 and 5.0 mg/kg, respectively) compared with post-pubertal shams (150 and 220% baseline for 2.5 and 5.0 mg/kg, respectively). Most interestingly, while prefrontal cortical perfusion of SKF 81297 (100 and 250 µm) had no significant effect on ACh release in post-pubertal sham-operated animals, it significantly stimulated ACh release to approximately 250% baseline at both doses in post-pubertal NVH-lesioned animals. Receptor autoradiography demonstrated a significant and selective increase in M1-like receptor binding sites in the infralimbic area of the PFC in the post-pubertal NVH-lesioned animals. For all experiments, significant differences between sham and NVH-lesioned animals were observed only in post-pubertal rats. These results suggest a developmentally specific reorganization of the prefrontal cortical cholinergic system involving D1-like receptors in the NVH model.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been demonstrated that not only do rats neonatally lesioned in the ventral hippocampus (VH) develop behavioural hypersensitivity to amphetamine postpubertally, but also that the expression of the sensitivity is strain specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to significant increases in amphetamine-induced locomotion in postpubertal Fischer rats, but not in Lewis rats. However, as it is likely that the effect of strain differences are due to a combination of genetics and environment, we examined the contributions of the environment of the pups in determining the behavioural outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross-fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic acid. anova analysis of postpubertal amphetamine-induced locomotor data revealed a significant effect of the strain of the dams raising the pups but no effect of the strain of the pup. In addition, a post hoc analysis revealed that lesioned Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned controls. Observations of the maternal behaviour of Fischer and Lewis dams revealed significant differences in the frequency of arched-back nursing between the two strains. Interestingly, a correlation of the frequency of arched back nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned rats were significantly more affected by increases in arched-back nursing compared to the controls. The results suggest that the genetic background of the pups does not significantly affect the behavioural outcome following neonatal VH lesions; however, the results do suggest an important role of early environmental variables on the behavioural outcome of neonatal VH lesions.
    Type of Medium: Electronic Resource
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