Abstract
AbstractMetabotropic glutamate receptor 5 (mGluR5) null mutant (-/-) mice have been reported to totally lack the reinforcing or locomotor stimulating effects of cocaine. We tested mGluR5 -/- and +/+ mice for their locomotor and conditioned place- preference response to cocaine. Unlike the previous finding, here we show that compared to mGluR5 +/+ mice, -/- mice exhibit no difference in the locomotor response to low to moderate doses of cocaine (10 or 20 mg/kg). A high dose of cocaine (40 mg/kg) resulted in a blunted rather than absent locomotor response. We tested mGluR5 -/- and +/+ mice for conditioned place-preference to cocaine and found no group differences at a conditioning dose of 10 mg/kg, suggesting normal conditioned rewarding properties of cocaine. These results differ substantially from Chiamulera et al. (2001) and replicates Olsen et al., (2010), who found normal cocaine place-preference in mGluR5 -/- mice at 5 mg/kg. Our results indicate mGluR5 receptors exert a modulatory rather than necessary role in cocaine-induced locomotor stimulation and exert no effect on the conditioned rewarding effects of cocaine.
Highlights
Metabotropic glutamate receptor 5 is Gq-coupled and, when activated by glutamate, initiates a signaling cascade that increases phospholipase C (PLC) and elevates intracellular Ca2+ from the endoplasmic reticulum which culminates in the activation of nonselective cation TRPC4/5 currents[1,2]
They reported a total lack of cocaine self-administration (SA) across all doses (0.08 -3.2 mg/kg i.v.) in the -/- mice despite normal responding for sucrose reward
It would appear from this study that cocaine is not acutely rewarding in mice lacking the Metabotropic glutamate receptor 5 (mGluR5) receptor, it may be that the conditioned rewarding effects of cocaine are intact
Summary
Metabotropic glutamate receptor 5 (mGluR5) is Gq-coupled and, when activated by glutamate, initiates a signaling cascade that increases phospholipase C (PLC) and elevates intracellular Ca2+ from the endoplasmic reticulum which culminates in the activation of nonselective cation TRPC4/5 currents[1,2]. Expression of mGluR5 in the brain is widespread, with some of the highest expression in the hippocampus, prefrontal cortex and striatum These areas are important for mediating the behavioral responses to psychostimulant drugs. The most compelling support for a necessary role for mGluR5 in cocaine mediated behaviors came from Chiamulera et al (2001) who used mGluR5 null mutant (-/-) mice to test the locomotor activating and rewarding properties of cocaine[4]. These authors reported a complete absence of locomotor response across a wide dose response range (10-40 mg/kg, i.p.) in the mGluR5 -/- mice[3]. To examine whether mGluR5 is necessary for this type of cocaine mediated reward we tested CPP in +/+ and -/- mice
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