Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine

Kim, Jee Hyun, Lavan, Doron, Chen, Nicola, Flores, Cecilia, Cooper, Helen and Lawrence, Andrew J. (2013) Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine. Psychopharmacology, 230 4: 607-616. doi:10.1007/s00213-013-3187-5


Author Kim, Jee Hyun
Lavan, Doron
Chen, Nicola
Flores, Cecilia
Cooper, Helen
Lawrence, Andrew J.
Title Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine
Journal name Psychopharmacology   Check publisher's open access policy
ISSN 0033-3158
1432-2072
Publication date 2013-12
Sub-type Article (original research)
DOI 10.1007/s00213-013-3187-5
Open Access Status
Volume 230
Issue 4
Start page 607
End page 616
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2014
Language eng
Formatted abstract
Rationale: The mesocorticolimbic dopamine system undergoes significant reorganization of neuronal connectivity and functional refinement during adolescence. Deleted in colorectal cancer (DCC), a receptor for the guidance cue netrin-1, is involved in this reorganization. Previous studies have shown that adult mice with a heterozygous (het) loss-of-function mutation in DCC exhibit impairments in sensitization and conditioned place preference (CPP) to psychostimulants. However, the commonly abused psychostimulant methamphetamine (METH) has not been assessed, and the role of DCC in drug self-administration remains to be established.

Objectives: Using dcc het mice and wildtype (WT) littermates, we extended previous findings on dcc haplodeficiency by examining self-administration of METH in adult mice, including cue-induced drug seeking following abstinence. We also examined hyperactivity, sensitization, and CPP to a METH-paired context in adult and adolescent mice.

Results: While adult dcc het mice expressed largely similar METH self-administration and cue-induced drug seeking as WT littermates, they failed to modulate responding according to dose of METH. Compared to WT, both adult and adolescent dcc het mice expressed impaired locomotor hyperactivity to acute METH but nevertheless showed comparable behavioral sensitization. Conditioned hyperactivity increased with age in WT but not in dcc het mice.

Conclusions: Impaired METH-induced hyperactivity and dose-related responding in adult dcc het mice suggest that reduced DCC alters METH-related behaviors. Adolescence is identified as a vulnerable period during which impairment in hyperactivity due to reduced DCC can be overcome with repeated METH injections. Nevertheless, DCC appears to have a somewhat limited role in METH-consumption and seeking following abstinence.
Keyword Methamphetamine
Self-administration
Conditioning
Mouse
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 3 July 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Created: Fri, 02 Aug 2013, 10:12:23 EST by Debra McMurtrie on behalf of Queensland Brain Institute