Metabotropic glutamate type 5 receptor binding availability during dextroamphetamine sensitization in mice and humans.
J Psychiatry Neurosci
; 46(1): E1-E13, 2021 01 04.
Article
en En
| MEDLINE
| ID: mdl-32559027
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 [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 neur.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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Desempeño Psicomotor
/
Corteza Prefrontal
/
Cuerpo Estriado
/
Dextroanfetamina
/
Sensibilización del Sistema Nervioso Central
/
Receptor del Glutamato Metabotropico 5
/
Estimulantes del Sistema Nervioso Central
/
Locomoción
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Psychiatry Neurosci
Asunto de la revista:
NEUROLOGIA
/
PSIQUIATRIA
Año:
2021
Tipo del documento:
Article