Metabotropic glutamate type 5 receptor binding availability during dextroamphetamine sensitization in mice and humans
Open Access
- 1 January 2021
- journal article
- research article
- Published by CMA Impact Inc. in Journal of Psychiatry and Neuroscience
- Vol. 46 (1), E1-E13
- https://doi.org/10.1503/jpn.190162
Abstract
Background Glutamate transmission is implicated in drug-induced behavioural sensitization and the associated long-lasting increases in mesolimbic output. Metabotropic glutamate type 5 (mGlu5) receptors might be particularly important, but most details are poorly understood. Methods We first assessed in mice (n = 51, all male) the effects of repeated dextroamphetamine administration (2.0 mg/kg, i.p.) on locomotor activity and binding of the mGlu5 ligand [H-3]ABP688. In a parallel study, in 19 stimulant-drug-naive healthy human volunteers (14 female) we administered 3 doses of dextroamphetamine (0.3 mg/kg, p.o.) or placebo, followed by a fourth dose 2 weeks later. We measured [C-11]ABP688 binding using positron emission tomography before and after the induction phase. We assessed psychomotor and behavioural sensitization using speech rate, eye blink rate and self-report. We measured the localization of mGlu5 relative to synaptic markers in mouse striatum using immunofluorescence. Results We observed amphetamine-induced psychomotor sensitization in mice and humans. We did not see group differences in mGlu5 availability following 3 pre-challenge amphetamine doses, but group differences did develop in mice administered 5 doses. In mice and humans, individual differences in mGlu5 binding after repeated amphetamine administration were negatively correlated with the extent of behavioural sensitization. In drug-naive mice, mGlu5 was expressed at 67% of excitatory synapses on dendrites of striatal medium spiny neurons. Limitations Correlational results should be interpreted as suggestive because of the limited sample size. We did not assess sex differences. Conclusion Together, these results suggest that changes in mGlu5 availability are not part of the earliest neural adaptations in stimulant-induced behavioural sensitization, but low mGlu5 binding might identify a higher propensity for sensitization.Keywords
This publication has 62 references indexed in Scilit:
- Limbic system mGluR5 availability in cocaine dependent subjects: A high-resolution PET [11C]ABP688 studyNeuroImage, 2014
- Dopamine ups and downs in vulnerability to addictions: a neurodevelopmental modelTrends in Pharmacological Sciences, 2014
- The mGlu5 receptor regulates extinction of cocaine-driven behavioursDrug and Alcohol Dependence, 2014
- Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance SpectroscopyBiological Psychiatry, 2013
- Drug-Evoked Synaptic Plasticity in Addiction: From Molecular Changes to Circuit RemodelingNeuron, 2011
- Quantifying talk: developing reliable measures of verbal productivityBehavior Research Methods, 2010
- Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant miceNature Neuroscience, 2001
- Localization of mGluR1a-like immunoreactivity and mGluR5-like immunoreactivity in identified populations of striatal neuronsBrain Research, 1998
- Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosisBrain Research, 1986
- Behavioral sensitization: Characterization of enduring changes in rotational behavior produced by intermittent injections of amphetamine in male and female ratsPsychopharmacology, 1984