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Animal Models

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Animal Model: Neonatal Ventral Hippocampal Lesion
Preparation Type: Lesion Preparations
DA-related behavior: Enhanced locomotor responses to amphetamine with post-pubertal onset; enhanced meth-amphetamine self-administration
Gating: Disrupted PPI; prolonged N40 latency
Cognitive behavior: Various impairments in learning and memory (including set-shifting and spatial working memory)
Social behavior: Impaired social behavior
Molecular/morphological signature: Reduced presynaptic protein and growth factor expression, reduced NMDA receptor expression, impaired DA receptor expression in frontal cortex; impaired maturation of PFC; brain region- and age-specific changes in GABAA receptor expression; reduced PFC spine density; enhanced sensitivity to nicotine; increased prefrontal DA output
Response to APD: Locomotor responses blocked by APD, social impairments blocked by clozapine but not haloperidol; clozapine reversed enhanced novelty-induced locomotor activity and rescued neuronal atrophy in the prefrontal cortex and nucleus accumbens
Citations: Lipska BK, Weinberger DR. To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology . 2000 Sep 1 ; 23(3):223-39. Abstract

Lipska BK. Using animal models to test a neurodevelopmental hypothesis of schizophrenia. J Psychiatry Neurosci . 2004 Jul ; 29(4):282-6. Abstract

Tseng KY, Amin F, Lewis BL, O'Donnell P. Altered prefrontal cortical metabolic response to mesocortical activation in adult animals with a neonatal ventral hippocampal lesion. Biol Psychiatry . 2006 Sep 15 ; 60(6):585-90. Abstract

Tseng KY, Lewis BL, Lipska BK, O'Donnell P. Post-pubertal disruption of medial prefrontal cortical dopamine-glutamate interactions in a developmental animal model of schizophrenia. Biol Psychiatry . 2007 Oct 1 ; 62(7):730-8. Abstract

Tseng KY, Lewis BL, Hashimoto T, Sesack SR, Kloc M, Lewis DA, O'Donnell P. A neonatal ventral hippocampal lesion causes functional deficits in adult prefrontal cortical interneurons. J Neurosci . 2008 Nov 26 ; 28(48):12691-9. Abstract

Endo K, Hori T, Abe S, Asada T. Alterations in GABA(A) receptor expression in neonatal ventral hippocampal lesioned rats: comparison of prepubertal and postpubertal periods. Synapse . 2007 Jun 1 ; 61(6):357-66. Abstract

Marquis JP, Goulet S, Doré FY. Neonatal ventral hippocampus lesions disrupt extra-dimensional shift and alter dendritic spine density in the medial prefrontal cortex of juvenile rats. Neurobiol Learn Mem . 2008 Sep 1 ; 90(2):339-46. Abstract

Brady AM, McCallum SE, Glick SD, O'Donnell P. Enhanced methamphetamine self-administration in a neurodevelopmental rat model of schizophrenia. Psychopharmacology (Berl) . 2008 Oct 1 ; 200(2):205-15. Abstract

Berg SA, Chambers RA. Accentuated behavioral sensitization to nicotine in the neonatal ventral hippocampal lesion model of schizophrenia. Neuropharmacology . 2008 Jun 1 ; 54(8):1201-7. Abstract

Brady AM. Neonatal ventral hippocampal lesions disrupt set-shifting ability in adult rats. Behav Brain Res . 2009 Dec 14 ; 205(1):294-8. Abstract

Vohs JL, Chambers RA, Krishnan GP, O'Donnell BF, Hetrick WP, Kaiser ST, Berg S, Morzorati SL. Auditory sensory gating in the neonatal ventral hippocampal lesion model of schizophrenia. Neuropsychobiology . 2009 ; 60(1):12-22. Abstract

Brady AM, Saul RD, Wiest MK. Selective deficits in spatial working memory in the neonatal ventral hippocampal lesion rat model of schizophrenia. Neuropharmacology . 2010 Dec ; 59(7-8):605-11. Abstract

Macedo CE, Angst MJ, Gobaille S, Schleef C, Guignard B, Guiberteau T, Louilot A, Sandner G. Prefrontal dopamine release and sensory-specific satiety altered in rats with neonatal ventral hippocampal lesions. Behav Brain Res . 2012 May 16 ; 231(1):97-104. Abstract


April 24, 2014
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