Format

Send to

Choose Destination
Neuropsychopharmacology. 2011 Mar;36(4):782-92. doi: 10.1038/npp.2010.212. Epub 2010 Dec 8.

Loss of object recognition memory produced by extended access to methamphetamine self-administration is reversed by positive allosteric modulation of metabotropic glutamate receptor 5.

Author information

1
Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.

Abstract

Chronic methamphetamine (meth) abuse can lead to persisting cognitive deficits. Here, we utilized a long-access meth self-administration (SA) protocol to assess recognition memory and metabotropic glutamate receptor (mGluR) expression, and the possible reversal of cognitive impairments with the mGluR5 allosteric modulator, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB). Male, Long-Evans rats self-administered i.v. meth (0.02 mg/infusion) on an FR1 schedule of reinforcement or received yoked-saline infusions. After seven daily 1-h sessions, rats were switched to 6-h daily sessions for 14 days, and then underwent drug abstinence. Rats were tested for object recognition memory at 1 week after meth SA at 90 min and 24 h retention intervals. In a separate experiment, rats underwent the same protocol, but received either vehicle or CDPPB (30 mg/kg) after familiarization. Rats were killed on day 8 or 14 post-SA and brain tissue was obtained. Meth intake escalated over the extended access period. Additionally, meth-experienced rats showed deficits in both short- and long-term recognition memory, demonstrated by a lack of novel object exploration. The deficit at 90 min was reversed by CDPPB treatment. On day 8, meth intake during SA negatively correlated with mGluR expression in the perirhinal and prefrontal cortex, and mGluR5 receptor expression was decreased 14 days after discontinuation of meth. This effect was specific to mGluR5 levels in the perirhinal cortex, as no differences were identified in the hippocampus or in mGluR2/3 receptors. These results from a clinically-relevant animal model of addiction suggest that mGluR5 receptor modulation may be a potential treatment of cognitive dysfunction in meth addiction.

PMID:
21150906
PMCID:
PMC3052905
DOI:
10.1038/npp.2010.212
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center