Tetrahydrobiopterin administration facilitates amphetamine-induced dopamine release and motivation in mice
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EN
Article de revue
Este ítem está publicado en
Behavioural Brain Research. 2020-02-03, vol. 379, p. 112348
Resumen en inglés
Dopamine (DA) is a critical neurotransmitter involved in motivational processes. Tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase, the rate-limiting enzyme in DA synthesis. Decreases in BH4 levels ...Leer más >
Dopamine (DA) is a critical neurotransmitter involved in motivational processes. Tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase, the rate-limiting enzyme in DA synthesis. Decreases in BH4 levels are observed in several DA-related neuropsychiatric diseases involving impairment in motivation. Yet, whether BH4 could be used to treat motivational deficits has not been comprehensively investigated. To investigate the effects of exogenous BH4 administration on the dopaminergic system and related behaviors, we acutely injected mice with BH4 (50 mg/kg). Passage of BH4 through the blood brain barrier and accumulation in brain was measured using the in situ brain perfusion technique. DA release was then recorded using in-vivo micro-dialysis and motivation was evaluated through operant conditioning paradigms in basal condition and after an amphetamine (AMPH) injection. First, we showed that BH4 crosses the blood-brain barrier and that an acute peripheral injection of BH4 is sufficient to increase the concentrations of biopterins in the brain, without affecting BH4- and DA-related protein expression. Second, we report that this increase in BH4 enhanced AMPH-stimulated DA release in the nucleus accumbens. Finally, we found that BH4-induced DA release led to improved performance of a motivational task. Altogether, these findings suggest that BH4, through its action on the dopaminergic tone, could be used as a motivational enhancer.< Leer menos
Palabras clave en inglés
Dopamine
Mice
Motivation
Tetrahydrobiopterin (BH4)
Proyecto europeo
Program Initiative d’Excellence
Proyecto ANR
Impact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivation - ANR-16-CE16-0022
Centros de investigación