The mGluR2/3 agonist LY379268 induced anti-reinstatement effects in rats exhibiting addiction-like behavior.
Neuropsychopharmacol. 2013-04-29; 38(10): 2048-2056
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1. Neuropsychopharmacology. 2013 Sep;38(10):2048-56. doi: 10.1038/npp.2013.106. Epub
2013 Apr 29.
The mGluR2/3 agonist LY379268 induced anti-reinstatement effects in rats
exhibiting addiction-like behavior.
Cannella N(1), Halbout B, Uhrig S, Evrard L, Corsi M, Corti C, Deroche-Gamonet V,
Hansson AC, Spanagel R.
(1)Institute of Psychopharmacology, Central Institute of Mental Health, Faculty
of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.
Medication development for cocaine-addicted patients is difficult, and many
promising preclinical candidates have failed in clinical trials. One reason for
the difficulty in translating preclinical findings to the human condition is that
drug testing is typically conducted in behavioral procedures in which animals do
not show addiction-like traits. Recently, a DSM-IV-based animal model has been
developed that allows studying the transition to an addiction-like behavior.
Changes in synaptic plasticity are involved in the transition to cocaine
addiction. In particular, it has been shown that metabotropic glutamate receptor
2/3 (mGluR2/3)-mediated long-term depression is suppressed in the prelimbic
cortex in addict-like rats. We therefore hypothesized that cocaine-seeking in
addict-like rats could be treated with an mGluR2/3 agonist. Indeed, addict-like
rats that were treated systemically with the mGluR2/3 agonist LY379268 (0, 0.3,
and 3 mg/kg) showed a pronounced reduction in cue-induced reinstatement of
cocaine-seeking. In an attempt to dissect the role played by mGluR2 and mGluR3 in
cue-induced reinstatement, we analyzed the mRNA expression patterns in several
relevant brain areas but did not find any significant differences between cocaine
addict-like and non-addict-like rats, suggesting that the behavioral differences
observed are due to translational rather than transcriptional regulation. Another
possibility to study the contributions of mGluR2 and mGluR3 in mediating
addictive-like behavior is the use of knockout models. Because mGluR2 knockouts
cannot be used in operant procedures due to motoric impairment, we only tested
mGluR3 knockouts. These mice did not differ from controls in reinstatement,
suggesting that mGluR2 receptors are critical in mediating addictive-like
PMID: 23624743 [Indexed for MEDLINE]