Neonatal Disconnection of the Rat Hippocampus: a Neurodevelopmental Model of Schizophrenia

Overview

Journal Dialogues Clin Neurosci

Specialty Neurology

Date 2011 Oct 29

PMID 22034469

Citations 2

Authors

Barbara K Lipska

Affiliations

Soon will be listed here.

Abstract

In the context of our current knowledge about schizophrenia, heuristic models of psychiatric disorders may be used to test the plausibility of theories developed on the basis of new emerging biological findings, explore mechanisms of schizophrenia-like phenomena, and develop potential new treatments. In a series of studies, we have shown that neonatal excitotoxic lesions of the rat ventral hippocampus (VH) may serve as a heuristic model. The model appears to mimic a spectrum of neurobiological and behavioral features of schizophrenia, including functional pathology in presumably critical brain regions interconnected with the hippocampal formation and targeted by antipsychotic drugs (the striatum/nucleus accumbens and the prefrontal cortex), and leads in adolescence or early adulthood to the emergence of abnormalities in a number of dopamine-related behaviors. Moreover, our data show that even transient inactivation of the VH during a critical period of development, which produces subtle, if any, anatomical changes in the hippocampus, may be sufficient to disrupt normal maturation of the prefrontal cortex (and perhaps, other interconnected latematuring regions) and trigger behavioral changes similar to those observed in animals with the permanent excitotoxic lesion. These results represent a potential new model of aspects of schizophrenia without a gross anatomical lesion.

Citing Articles

Polymorphism in the ZNF804A Gene and Variation in D and D/D Dopamine Receptor Availability in the Healthy Human Brain: A Dual Positron Emission Tomography Study.

Hegarty C, Ianni A, Kohn P, Kolachana B, Gregory M, Masdeu J Biol Psychiatry Cogn Neurosci Neuroimaging. 2021; 8(1):121-128.

PMID: 33712377 PMC: 10501410. DOI: 10.1016/j.bpsc.2020.12.006.

Physical activity level and medial temporal health in youth at ultra high-risk for psychosis.

Mittal V, Gupta T, Orr J, Pelletier-Baldelli A, Dean D, Lunsford-Avery J J Abnorm Psychol. 2013; 122(4):1101-10.

PMID: 24364613 PMC: 3891894. DOI: 10.1037/a0034085.

References

Falkai P, Bogerts B . Cell loss in the hippocampus of schizophrenics. Eur Arch Psychiatry Neurol Sci. 1986; 236(3):154-61. DOI: 10.1007/BF00380943. View

Castner S, Baldwin R, Seibyl J, Innis R, Goldman-Rakic P . Behavioral changes and [123I]IBZM equilibrium SPECT measurement of amphetamine-induced dopamine release in rhesus monkeys exposed to subchronic amphetamine. Neuropsychopharmacology. 2000; 22(1):4-13. DOI: 10.1016/S0893-133X(99)00080-9. View

Saunders R, Kolachana B, Bachevalier J, Weinberger D . Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine. Nature. 1998; 393(6681):169-71. DOI: 10.1038/30245. View

Lipska B, Aultman J, Verma A, Weinberger D, Moghaddam B . Neonatal damage of the ventral hippocampus impairs working memory in the rat. Neuropsychopharmacology. 2002; 27(1):47-54. DOI: 10.1016/S0893-133X(02)00282-8. View

Lipska B, Chrapusta S, Egan M, Weinberger D . Neonatal excitotoxic ventral hippocampal damage alters dopamine response to mild repeated stress and to chronic haloperidol. Synapse. 1995; 20(2):125-30. DOI: 10.1002/syn.890200205. View

Sams-Dodd F, Lipska B, Weinberger D . Neonatal lesions of the rat ventral hippocampus result in hyperlocomotion and deficits in social behaviour in adulthood. Psychopharmacology (Berl). 1997; 132(3):303-10. DOI: 10.1007/s002130050349. View

Beauregard M, Bachevalier J . Neonatal insult to the hippocampal region and schizophrenia: a review and a putative animal model. Can J Psychiatry. 1996; 41(7):446-56. DOI: 10.1177/070674379604100710. View

Lipska B, Al-Amin H, Weinberger D . Excitotoxic lesions of the rat medial prefrontal cortex. Effects on abnormal behaviors associated with neonatal hippocampal damage. Neuropsychopharmacology. 1998; 19(6):451-64. DOI: 10.1016/S0893-133X(98)00045-1. View

Imperato A, Obinu M, Carta G, Mascia M, Casu M, Gessa G . Reduction of dopamine release and synthesis by repeated amphetamine treatment: role in behavioral sensitization. Eur J Pharmacol. 1996; 317(2-3):231-7. DOI: 10.1016/s0014-2999(96)00742-x. View

10.

Grecksch G, Bernstein H, Becker A, Hollt V, Bogerts B . Disruption of latent inhibition in rats with postnatal hippocampal lesions. Neuropsychopharmacology. 1999; 20(6):525-32. DOI: 10.1016/S0893-133X(98)00081-5. View

11.

Meng Z, Feldpaush D, Merchant K . Clozapine and haloperidol block the induction of behavioral sensitization to amphetamine and associated genomic responses in rats. Brain Res Mol Brain Res. 1998; 61(1-2):39-50. DOI: 10.1016/s0169-328x(98)00196-x. View

12.

Jay T, Glowinski J, Thierry A . Selectivity of the hippocampal projection to the prelimbic area of the prefrontal cortex in the rat. Brain Res. 1989; 505(2):337-40. DOI: 10.1016/0006-8993(89)91464-9. View

13.

Lipska B, Weinberger D . To model a psychiatric disorder in animals: schizophrenia as a reality test. Neuropsychopharmacology. 2000; 23(3):223-39. DOI: 10.1016/S0893-133X(00)00137-8. View

14.

Lipska B, Swerdlow N, Geyer M, Jaskiw G, Braff D, Weinberger D . Neonatal excitotoxic hippocampal damage in rats causes post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine. Psychopharmacology (Berl). 1995; 122(1):35-43. DOI: 10.1007/BF02246439. View

15.

Weinberger D . Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987; 44(7):660-9. DOI: 10.1001/archpsyc.1987.01800190080012. View

16.

Wan R, Hartman H, Corbett R . Alteration of dopamine metabolites in CSF and behavioral impairments induced by neonatal hippocampal lesions. Physiol Behav. 1999; 65(3):429-36. DOI: 10.1016/s0031-9384(98)00179-6. View

17.

Al-Amin H, Weickert C, Weinberger D, Lipska B . Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus. Biol Psychiatry. 2001; 49(6):528-39. DOI: 10.1016/s0006-3223(00)00968-9. View

18.

Jeste D, Lohr J . Hippocampal pathologic findings in schizophrenia. A morphometric study. Arch Gen Psychiatry. 1989; 46(11):1019-24. DOI: 10.1001/archpsyc.1989.01810110061009. View

19.

Breier A, Su T, Saunders R, Carson R, Kolachana B, de Bartolomeis A . Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A. 1997; 94(6):2569-74. PMC: 20129. DOI: 10.1073/pnas.94.6.2569. View

20.

Lieberman J, Sheitman B, Kinon B . Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology. 1997; 17(4):205-29. DOI: 10.1016/S0893-133X(97)00045-6. View