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Neuregulin 1 hypomorphic mutant mice: enhanced baseline locomotor activity but normal psychotropic drug-induced hyperlocomotion and prepulse inhibition regulation.
Int J Neuropsychopharmacol. 2009 Nov; 12(10):1383-93.IJ

Abstract

Neuregulin 1 (Nrg1) has been widely recognized as a candidate gene for schizophrenia. This study therefore investigated mice heterozygous for a mutation in the transmembrane domain of this trophic factor (Nrg1+/- mice) in a number of behavioural test systems with relevance to schizophrenia, including psychotropic drug-induced locomotor hyperactivity and prepulse inhibition (PPI) of startle. Baseline locomotor activity in the open field or in photocell cages was slightly, but significantly enhanced in Nrg1+/- mice compared to wild-type littermate controls at age 12-16 wk, but not at age 6 months. The ability of amphetamine, phencyclidine (PCP) or MK-801 to induce locomotor hyperactivity was not significantly different between the genotypes. There was no difference in baseline PPI, startle or startle habituation and there was no difference in the effect of apomorphine, amphetamine or MK-801 on any of these parameters. Only treatment with the 5-HT1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) showed a differential effect between genotypes, with a disruption of PPI occurring in Nrg1+/- mice compared to no effect in wild-type controls. This treatment also induced a significant reduction of startle which could have influenced the result. The density of dopamine D2 receptors in the forebrain and of 5-HT1A receptors in the hippocampus and raphe nuclei was not different between Nrg1+/- mice and controls. These studies add to the knowledge about behavioural effects in this mouse model of impaired Nrg1 function and suggest that a number of the behavioural tests with relevance to schizophrenia are normal in these mice.

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Authors+Show Affiliations

van den Buuse M
Behavioural Neuroscience Laboratory, Mental Health Research Institute, Melbourne, Australia. m.vandenbuuse@mhri.edu.au
Wischhof L
No affiliation info available
Lee RX
No affiliation info available
Martin S
No affiliation info available
Karl T
No affiliation info available

MeSH

Acoustic StimulationAnimalsDose-Response Relationship, DrugHyperkinesisMaleMiceMice, Mutant StrainsMotor ActivityNeuregulin-1Psychotropic DrugsReflex, Startle

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19400983

Citation

van den Buuse, Maarten, et al. "Neuregulin 1 Hypomorphic Mutant Mice: Enhanced Baseline Locomotor Activity but Normal Psychotropic Drug-induced Hyperlocomotion and Prepulse Inhibition Regulation." The International Journal of Neuropsychopharmacology, vol. 12, no. 10, 2009, pp. 1383-93.
van den Buuse M, Wischhof L, Lee RX, et al. Neuregulin 1 hypomorphic mutant mice: enhanced baseline locomotor activity but normal psychotropic drug-induced hyperlocomotion and prepulse inhibition regulation. Int J Neuropsychopharmacol. 2009;12(10):1383-93.
van den Buuse, M., Wischhof, L., Lee, R. X., Martin, S., & Karl, T. (2009). Neuregulin 1 hypomorphic mutant mice: enhanced baseline locomotor activity but normal psychotropic drug-induced hyperlocomotion and prepulse inhibition regulation. The International Journal of Neuropsychopharmacology, 12(10), 1383-93. https://doi.org/10.1017/S1461145709000388
van den Buuse M, et al. Neuregulin 1 Hypomorphic Mutant Mice: Enhanced Baseline Locomotor Activity but Normal Psychotropic Drug-induced Hyperlocomotion and Prepulse Inhibition Regulation. Int J Neuropsychopharmacol. 2009;12(10):1383-93. PubMed PMID: 19400983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuregulin 1 hypomorphic mutant mice: enhanced baseline locomotor activity but normal psychotropic drug-induced hyperlocomotion and prepulse inhibition regulation. AU - van den Buuse,Maarten, AU - Wischhof,Lena, AU - Lee,Ruo Xi, AU - Martin,Sally, AU - Karl,Tim, Y1 - 2009/04/29/ PY - 2009/4/30/entrez PY - 2009/4/30/pubmed PY - 2010/6/30/medline SP - 1383 EP - 93 JF - The international journal of neuropsychopharmacology JO - Int J Neuropsychopharmacol VL - 12 IS - 10 N2 - Neuregulin 1 (Nrg1) has been widely recognized as a candidate gene for schizophrenia. This study therefore investigated mice heterozygous for a mutation in the transmembrane domain of this trophic factor (Nrg1+/- mice) in a number of behavioural test systems with relevance to schizophrenia, including psychotropic drug-induced locomotor hyperactivity and prepulse inhibition (PPI) of startle. Baseline locomotor activity in the open field or in photocell cages was slightly, but significantly enhanced in Nrg1+/- mice compared to wild-type littermate controls at age 12-16 wk, but not at age 6 months. The ability of amphetamine, phencyclidine (PCP) or MK-801 to induce locomotor hyperactivity was not significantly different between the genotypes. There was no difference in baseline PPI, startle or startle habituation and there was no difference in the effect of apomorphine, amphetamine or MK-801 on any of these parameters. Only treatment with the 5-HT1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) showed a differential effect between genotypes, with a disruption of PPI occurring in Nrg1+/- mice compared to no effect in wild-type controls. This treatment also induced a significant reduction of startle which could have influenced the result. The density of dopamine D2 receptors in the forebrain and of 5-HT1A receptors in the hippocampus and raphe nuclei was not different between Nrg1+/- mice and controls. These studies add to the knowledge about behavioural effects in this mouse model of impaired Nrg1 function and suggest that a number of the behavioural tests with relevance to schizophrenia are normal in these mice. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/19400983/Neuregulin_1_hypomorphic_mutant_mice:_enhanced_baseline_locomotor_activity_but_normal_psychotropic_drug_induced_hyperlocomotion_and_prepulse_inhibition_regulation_ L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145709000388 DB - PRIME DP - Unbound Medicine ER -