RT Journal Article SR Electronic T1 Metabotropic glutamate type 5 receptor binding availability during dextroamphetamine sensitization in mice and humans JF Journal of Psychiatry and Neuroscience JO JPN FD Canadian Medical Association SP E1 OP E13 DO 10.1503/jpn.190162 VO 46 IS 1 A1 Kelly Smart A1 Atsuko Nagano-Saito A1 Michele S. Milella A1 Diana Yae Sakae A1 Mathieu Favier A1 Erika Vigneault A1 Leanne Louie A1 Alison Hamilton A1 Stephen S.G. Ferguson A1 Pedro Rosa-Neto A1 Sridar Narayanan A1 Salah El Mestikawy A1 Marco Leyton A1 Chawki Benkelfat YR 2021 UL http://jpn.ca/content/46/1/E1.abstract AB 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 [3H]ABP688. In a parallel study, in 19 stimulant-drug-naïve 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 [11C]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-naïve 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.