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Metabotropic glutamate type 5 receptor binding availability during dextroamphetamine sensitization in mice and humans
Kelly Smart1, Atsuko Nagano-Saito1, Michele S Milella1
1From the Department of Psychiatry, McGill University, Montreal, Que. (Smart, Nagano-Saito, Milella, Sakae, Favier, Vigneault, Louie, Rosa-Neto, El Mestikawy, Leyton, Benkelfat); the Douglas Mental Health University Institute, McGill University, Montreal, Que. (Smart, Sakae, Favier, Vigneault, Rosa-Neto, El Mestikawy); the Department of Cellular and Molecular Medicine, University of Ottawa, Ont. (Hamilton, Ferguson); the McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Que. (Rosa-Neto, Narayanan, Leyton, Benkelfat); the Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Que. (Rosa-Neto, Narayanan, Leyton, Benkelfat); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que. (Leyton).
Changes in metabotropic glutamate type 5 (mGlu5) receptor availability are not an early sign of stimulant-induced sensitization. However, lower mGlu5 binding may indicate a greater susceptibility to developing sensitization.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Glutamate neurotransmission plays a role in drug-induced behavioral sensitization and sustained increases in mesolimbic output.
- Metabotropic glutamate type 5 (mGlu5) receptors are potentially significant, yet their precise involvement remains unclear.
Purpose of the Study:
- To investigate the role of metabotropic glutamate type 5 (mGlu5) receptors in the development of stimulant-induced behavioral sensitization.
- To examine changes in mGlu5 receptor availability and their correlation with sensitization in both mouse and human models.
Main Methods:
- Repeated administration of dextroamphetamine in mice and humans to induce behavioral sensitization.
- Positron emission tomography (PET) with [11C]ABP688 to measure mGlu5 receptor availability.
- Assessment of psychomotor and behavioral sensitization through activity monitoring, speech rate, eye blink rate, and self-report.
Main Results:
- Amphetamine induced psychomotor sensitization in both mice and humans.
- No significant group differences in mGlu5 availability were observed after three amphetamine doses, but differences emerged in mice after five doses.
- Individual differences in mGlu5 binding after repeated amphetamine administration were inversely correlated with the degree of behavioral sensitization.
Conclusions:
- Changes in mGlu5 receptor availability are not among the initial neural adaptations in stimulant-induced behavioral sensitization.
- Reduced mGlu5 receptor binding may be an indicator of an increased propensity for developing sensitization.
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