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 null mutant (-/-) mice have been reported to totally lack the reinforcing or locomotor stimulating effects of cocaine
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]
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) null mutant (-/-) mice have been reported to totally lack the reinforcing or locomotor stimulating effects of cocaine. 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. 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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