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Adolescent neuregulin 1 heterozygous mice display enhanced behavioural sensitivity to methamphetamine.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 03; 39(2):376-81.PN

Abstract

Methamphetamine use triggers psychosis in genetically vulnerable individuals, however the exact nature of this genetic predisposition requires elucidation. In addition, adolescence may be a particular period of neurodevelopmental vulnerability to the actions of methamphetamine; interestingly, this period coincides with a higher likelihood of onset of schizophrenia and drug experimentation. In the current study we investigated whether adolescent mice heterozygous for the schizophrenia susceptibility gene neuregulin 1 (Nrg1 HET mice) exhibit altered behavioural responses to methamphetamine (0.6 or 2.4mg/kg) in schizophrenia-relevant paradigms. The responses measured were locomotor activity in the open field test and sensorimotor gating function in the prepulse inhibition of startle paradigm (PPI). Adolescent Nrg1 HET mice displayed a subtle, transient, novelty-induced baseline locomotor hyperactivity over days, and a selective PPI deficit at the prepulse intensity-interstimulus interval (ISI) combination of 82dB-64ms. Adolescent Nrg1 HET mice were more sensitive to the locomotor stimulatory effects of an acute, low-dose of methamphetamine (0.6mg/kg) relative to wild-type (WT) controls. The augmented response to acute methamphetamine observed in Nrg1 HET mice disappeared with repeated, daily dosing over 7days. Methamphetamine did not affect average PPI (total or across different prepulse intensities), however 0.6mg/kg methamphetamine triggered a PPI deficit selectively in Nrg1 HET mice but not WT mice at 82dB-256ms. Our results show that locomotor hyperactivity in Nrg1 HET mice, albeit subtle, can manifest much earlier than previously reported and that Nrg1 may confer vulnerability to the acute actions of methamphetamine, a drug known to trigger psychotic reactions in humans.

Authors+Show Affiliations

Discipline of Pharmacology, University of Sydney, NSW 2006, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22850204

Citation

Spencer, Jarrah R., et al. "Adolescent Neuregulin 1 Heterozygous Mice Display Enhanced Behavioural Sensitivity to Methamphetamine." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 39, no. 2, 2012, pp. 376-81.
Spencer JR, Darbyshire KM, Boucher AA, et al. Adolescent neuregulin 1 heterozygous mice display enhanced behavioural sensitivity to methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(2):376-81.
Spencer, J. R., Darbyshire, K. M., Boucher, A. A., & Arnold, J. C. (2012). Adolescent neuregulin 1 heterozygous mice display enhanced behavioural sensitivity to methamphetamine. Progress in Neuro-psychopharmacology & Biological Psychiatry, 39(2), 376-81. https://doi.org/10.1016/j.pnpbp.2012.07.014
Spencer JR, et al. Adolescent Neuregulin 1 Heterozygous Mice Display Enhanced Behavioural Sensitivity to Methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 3;39(2):376-81. PubMed PMID: 22850204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adolescent neuregulin 1 heterozygous mice display enhanced behavioural sensitivity to methamphetamine. AU - Spencer,Jarrah R, AU - Darbyshire,Keturah M E, AU - Boucher,Aurelie A, AU - Arnold,Jonathon C, Y1 - 2012/07/29/ PY - 2012/04/25/received PY - 2012/07/23/revised PY - 2012/07/23/accepted PY - 2012/8/2/entrez PY - 2012/8/2/pubmed PY - 2013/3/21/medline SP - 376 EP - 81 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog Neuropsychopharmacol Biol Psychiatry VL - 39 IS - 2 N2 - Methamphetamine use triggers psychosis in genetically vulnerable individuals, however the exact nature of this genetic predisposition requires elucidation. In addition, adolescence may be a particular period of neurodevelopmental vulnerability to the actions of methamphetamine; interestingly, this period coincides with a higher likelihood of onset of schizophrenia and drug experimentation. In the current study we investigated whether adolescent mice heterozygous for the schizophrenia susceptibility gene neuregulin 1 (Nrg1 HET mice) exhibit altered behavioural responses to methamphetamine (0.6 or 2.4mg/kg) in schizophrenia-relevant paradigms. The responses measured were locomotor activity in the open field test and sensorimotor gating function in the prepulse inhibition of startle paradigm (PPI). Adolescent Nrg1 HET mice displayed a subtle, transient, novelty-induced baseline locomotor hyperactivity over days, and a selective PPI deficit at the prepulse intensity-interstimulus interval (ISI) combination of 82dB-64ms. Adolescent Nrg1 HET mice were more sensitive to the locomotor stimulatory effects of an acute, low-dose of methamphetamine (0.6mg/kg) relative to wild-type (WT) controls. The augmented response to acute methamphetamine observed in Nrg1 HET mice disappeared with repeated, daily dosing over 7days. Methamphetamine did not affect average PPI (total or across different prepulse intensities), however 0.6mg/kg methamphetamine triggered a PPI deficit selectively in Nrg1 HET mice but not WT mice at 82dB-256ms. Our results show that locomotor hyperactivity in Nrg1 HET mice, albeit subtle, can manifest much earlier than previously reported and that Nrg1 may confer vulnerability to the acute actions of methamphetamine, a drug known to trigger psychotic reactions in humans. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/22850204/Adolescent_neuregulin_1_heterozygous_mice_display_enhanced_behavioural_sensitivity_to_methamphetamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(12)00187-X DB - PRIME DP - Unbound Medicine ER -