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Vol. 36, No. 1, 2014
Issue release date: March 2014
Section title: Original Paper
Dev Neurosci 2014;36:18-28
(DOI:10.1159/000357495)

Late-Life Effects of Chronic Methamphetamine Exposure during Puberty on Behaviour and Corticostriatal Mono-Amines in Social Isolation-Reared Rats

Strauss L. · Brink C.B. · Möller M. · Stein D.J. · Harvey B.H.
aDivision of Pharmacology, School of Pharmacy, and bCentre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, and cMRC Unit for Anxiety and Stress Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 4/24/2013 8:15:50 AM
Accepted: 11/21/2013
Published online: 1/24/2014

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 2

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE

Abstract

Chronic methamphetamine (MA) abuse results in an acute psychosis indistinguishable from paranoid schizophrenia. However, less is known of the interaction between MA use and environmental insults, and how this contributes to late-onset psychopathology. Using social isolation rearing (SIR), a neurodevelopmental animal model of schizophrenia, we investigated the association between changes in corticostriatal mono-amines and putative behaviours related to MA-induced psychosis in isolation and group-housed rats following chronic MA or saline exposure. Weaned male offspring of MA-naive female Wistar rats, either group- or isolation-housed from postnatal day (PND) +21, received saline (2 ml/kg s.c. b.i.d.) or an escalating dose of MA (0.2-6 mg/kg s.c. b.i.d.) for 16 days from PND +35 to +50. On PND +78, offspring were tested for deficits in social interactive behaviour (SIB) and prepulse inhibition (PPI) of startle, with frontal cortex and striatum harvested for the assessment of mono-amine concentrations. SIR significantly reduced rearing time, staying together, approaching and anogenital sniffing (outward-directed SIB), but increased self-grooming and locomotor activity (self-directed SIB), and also induced profound deficits in PPI. Pubertal MA exposure in group-housed animals also induced similar alterations in outward- and self-directed SIB and reduced PPI. Combined MA + SIR exposure evoked a similarly intense behavioural response as SIR or MA separately, with no exacerbation evident. Neither treatment separately nor together affected corticostriatal serotonin or noradrenaline levels, although frontal cortical dopamine (DA) levels were significantly increased in SIR and MA + group-housed animals. A trend towards further elevated frontal cortical DA was noted in the MA + SIR treatment group. Striatal DA was unaltered by all treatments. This study provides the first evidence that chronic pubertal MA exposure evokes postpubertal psychosis-like behaviours in rats of similar intensity to that induced by a neurodevelopmental animal model of schizophrenia (SIR). Moreover, the study is unique in that these behavioural changes occur together with associated changes in frontal cortical but not striatal DA, without affecting other mono-amines, and strongly implicates frontal cortical DA changes in the psychotogenic effects of early-life MA exposure or environmental insult. Although MA exposure in animals with a history of environmental insult (i.e. MA + SIR) has similar effects, combined exposure was not additive with regard to behavioural or neurochemical changes. We conclude that a ceiling effect or compensatory mechanisms prevent more pronounced neurobehavioural deficits occurring following MA + SIR treatment, at least under the current study conditions.


  

Author Contacts

Brian H. Harvey, PhD
Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy
Faculty of Health Sciences, North-West University
Potchefstroom, 2520 (South Africa)
E-Mail Brian.Harvey@nwu.ac.za

  

Article Information

Received: April 24, 2013
Accepted after revision: November 21, 2013
Published online: January 24, 2014
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 2, Number of References : 62

  

Publication Details

Developmental Neuroscience

Vol. 36, No. 1, Year 2014 (Cover Date: March 2014)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 4/24/2013 8:15:50 AM
Accepted: 11/21/2013
Published online: 1/24/2014

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 2

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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