Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission

Modafinil (MOD) is an atypical stimulant used to enhance wakefulness and vigilance. The mechanism of action of MOD includes the blockage of dopamine (DA) and norepinephrine (NE) transporters (DAT and NET, respectively). In humans, it has been demonstrated that MOD binds to DAT in nucleus accumbens (...

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Autor: Cid Jofré, Valeska Soledad
Tipo de documento: tese
Estado:Versão publicada
Data de publicação:2020
País:Chile
OAI Identifier:oai:repositorio.anid.cl:10533/249831
Acesso em linha:https://hdl.handle.net/10533/249831
Access Level:Acceso aberto
Palavra-chave:Ciencias Naturales
Otras Ciencias Médicas
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dc.title.es_CL.fl_str_mv Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
title Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
spellingShingle Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
Cid Jofré, Valeska Soledad
Ciencias Naturales
Otras Ciencias Médicas
title_short Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
title_full Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
title_fullStr Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
title_full_unstemmed Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
title_sort Effects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmission
dc.creator.none.fl_str_mv Cid Jofré, Valeska Soledad
author Cid Jofré, Valeska Soledad
author_facet Cid Jofré, Valeska Soledad
author_role author
dc.contributor.advisor.none.fl_str_mv Cruz Neculpan, Gonzalo
Renard, Georgina
dc.contributor.institution.es_CL.fl_str_mv UNIVERSIDAD DE VALPARAISO
dc.subject.oecd1n.es_CL.fl_str_mv Ciencias Naturales
topic Ciencias Naturales
Otras Ciencias Médicas
dc.subject.oecd2n.es_CL.fl_str_mv Otras Ciencias Médicas
description Modafinil (MOD) is an atypical stimulant used to enhance wakefulness and vigilance. The mechanism of action of MOD includes the blockage of dopamine (DA) and norepinephrine (NE) transporters (DAT and NET, respectively). In humans, it has been demonstrated that MOD binds to DAT in nucleus accumbens (NAc), an important nucleus in the reward circuitry. Moreover, studies have been shown a crucial role for glutamate (GLU) and γ-aminobutyric acid (GABA) in the reward circuitry in relation to drug addiction. Also, MOD administration modifies DA and GABA extracellular levels in NAc in naïve animals. Clinical trials are testing MOD for the treatment of attentional deficit hyperactivity disorder (ADHD) in children. In view of a reported over diagnostic of ADHD, evaluating the effects of MOD in healthy young individuals is crucial. Herein, we evaluated the effects of 14 days of MOD treatment in behavioural (social play behaviour and locomotor activity) and neurochemical measurements (content levels of DA, DOPAC, glutamate and GABA in NAc and VTA), moreover, we analyzed maximal DA uptake, extracellular DA levels and DA release in NAc and D2 expression in PFC and NAc after 14 days of treatment in young healthy rats. MOD altered and decreased the replies to play solicitations, additionally reduced the expression of D2 in PFC and the response of DAergic neurons in NAc after K+ 70 mM depolarizing stimulus. The lower responsiveness of DAergic terminals could be explained by the trend for high extracellular GABA basal levels and less inhibition of the glutamatergic projections in PFC due to lower expression of D2. To date, our results are the first evidence showing effects on social play behaviour and DA system within reward circuitry after 14 days of MOD treatment in young healthy individuals. Therefore, more data is needed to unravel the effects of MOD in the mesocorticolimbic circuitry in young individuals, specifically in key brain nuclei as NAc, VTA and PFC.
publishDate 2020
dc.date.issued.es_CL.fl_str_mv 2020
dc.date.accessioned.none.fl_str_mv 2021-06-14T18:43:22Z
2022-08-23T04:12:15Z
dc.date.available.none.fl_str_mv 2021-06-14T18:43:22Z
2022-08-23T04:12:15Z
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dc.type.tesis.none.fl_str_mv Tesis
format doctoralThesis
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spelling UNIVERSIDAD DE VALPARAISOCid Jofré, Valeska Soledad2020https://hdl.handle.net/10533/249831http://purl.org/coar/access_right/c_abf2Otras Ciencias MédicasCiencias NaturalesEffects of chronic modafinil treatment in young rats on social behaviour and dopaminergic neurotransmissionCruz Neculpan, GonzaloRenard, GeorginaUNIVERSIDAD DE VALPARAISOChileCid Jofré, Valeska Soledad2021-06-14T18:43:22Z2022-08-23T04:12:15Z2021-06-14T18:43:22Z2022-08-23T04:12:15Z2020Modafinil (MOD) is an atypical stimulant used to enhance wakefulness and vigilance. The mechanism of action of MOD includes the blockage of dopamine (DA) and norepinephrine (NE) transporters (DAT and NET, respectively). In humans, it has been demonstrated that MOD binds to DAT in nucleus accumbens (NAc), an important nucleus in the reward circuitry. Moreover, studies have been shown a crucial role for glutamate (GLU) and γ-aminobutyric acid (GABA) in the reward circuitry in relation to drug addiction. Also, MOD administration modifies DA and GABA extracellular levels in NAc in naïve animals. Clinical trials are testing MOD for the treatment of attentional deficit hyperactivity disorder (ADHD) in children. In view of a reported over diagnostic of ADHD, evaluating the effects of MOD in healthy young individuals is crucial. Herein, we evaluated the effects of 14 days of MOD treatment in behavioural (social play behaviour and locomotor activity) and neurochemical measurements (content levels of DA, DOPAC, glutamate and GABA in NAc and VTA), moreover, we analyzed maximal DA uptake, extracellular DA levels and DA release in NAc and D2 expression in PFC and NAc after 14 days of treatment in young healthy rats. MOD altered and decreased the replies to play solicitations, additionally reduced the expression of D2 in PFC and the response of DAergic neurons in NAc after K+ 70 mM depolarizing stimulus. The lower responsiveness of DAergic terminals could be explained by the trend for high extracellular GABA basal levels and less inhibition of the glutamatergic projections in PFC due to lower expression of D2. To date, our results are the first evidence showing effects on social play behaviour and DA system within reward circuitry after 14 days of MOD treatment in young healthy individuals. 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