Chronic modafinil administration to preadolescent rats impairs social play behavior and dopaminergic system

Cid-Jofré, Valeska; Gárate‐Pérez, Macarena F.; Clark, P. J.; Valero-Jara, Viviana; España, Rodrigo A.; Sotomayor‐Zárate, Ramón; Cruz, Gonzalo; Renard, Georgina M.

doi:10.1016/j.neuropharm.2020.108404

Cited by 7 publications

(12 citation statements)

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“…However, blocking ionotropic glutamate receptors in LS decreased social play only in females [ 44 ]. These results are contradictory to our previous results that showed a decrease in social play behavior after chronic MOD treatment [ 22 ] and the suggested increase in VTA GABA release. This discrepancy could be due to a different action of GABA in different nuclei.…”

Section: Discussioncontrasting

confidence: 99%

“…This different outcome in the GLU and GABAergic systems suggests that MOD exerts a region-specific effect on both neurotransmitters, and it probably depends on the type of treatment or administration (single versus repeated). As we showed in our results, GABA tissue levels were lower in the VTA in treated rats, and based on previous data in our laboratory, DA release was lower than the vehicle (see [ 22 ]) and GLU release did not change. Therefore, repeated MOD might increase the inhibitory balance in the NAc due to an augmentation of GABAergic communication with the VTA, and this enhancement of inhibitory balance is not because of a decrease in GLU levels.…”

Section: Discussionsupporting

confidence: 90%

“…This finding suggests an increase in GABA release in the VTA. Considering that GABA interneurons in the VTA regulate the firing of DA neurons [ 42 ], this result could explain our previous result in which the extracellular NAc DA levels were decreased after a depolarizing stimulus in the group treated with MOD [ 22 ]. We also observed higher extracellular NAc GABA levels after a 70 mM K + depolarizing stimulus compared to basal extracellular GABA levels in the MOD-treated group.…”

Section: Discussionmentioning

confidence: 77%

“…In previous research, we reported that chronic MOD treatment during preadolescence impairs social play behavior. This was associated to a lower extracellular DA level in the NAc in response to a depolarizing stimulus compared to the controls [ 22 ]. In the current study, we used the same protocol of 14 days of MOD treatment in preadolescent rats to elucidate if GLU and GABA levels in the mesolimbic pathway are involved in our previous results.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, acute and chronic MPH fails to increase locomotor activity when glutamatergic synapses are disrupted [ 20 , 21 ]. Recently, our group demonstrated that chronic MOD administration in adolescent male rats decreases DA release in the NAc [ 22 ], suggesting an impairment of the mesocorticolimbic system. However, the effects of the chronic use of this drug on glutamatergic and GABAergic transmission, especially in young healthy individuals, remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels

Cid-Jofré

Moreno

Sotomayor‐Zárate

et al. 2022

IJMS

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The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D2) expression and behavior (non-selective attention “NSA”) in the mesocorticolimbic system of young healthy Sprague–Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D2 protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D2 expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels

Cid-Jofré

Moreno

Sotomayor‐Zárate

et al. 2022

IJMS

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From molecular variations to behavioral adaptations: Unveiling adaptive epistasis in primate oxytocin system

Vargas‐Pinilla,

S. Oliveira Fam,

Medina Tavares

et al. 2024

American Journal of Biological Anthropology

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ObjectiveOur primary objective was to investigate the variability of oxytocin (OT) and the GAMEN binding motif within the LNPEP oxytocinase in primates.Materials and MethodsWe sequenced the LNPEP segment encompassing the GAMEN motif in 34 Platyrrhini species, with 21 of them also sequenced for the OT gene. Our dataset was supplemented with primate sequences of LNPEP, OT, and the oxytocin receptor (OTR) sourced from public databases. Evolutionary analysis and coevolution predictions were made followed by the macroevolution analysis of relevant amino acids associated with phenotypic traits, such as mating systems, parental care, and litter size. To account for phylogenetic structure, we utilized two distinct statistical tests. Additionally, we calculated binding energies focusing on the interaction between Callithtrix jacchus VAMEN and Pro8OT.ResultsWe identified two novel motifs (AAMEN and VAMEN), challenging the current knowledge of motif conservation in placental mammals. Coevolution analysis demonstrated a correlation between GAMEN, AAMEN, and VAMEN and their corresponding OTs and OTRs. Callithrix jacchus exhibited a higher binding energy between VAMEN and Pro8OT than orthologous molecules found in humans (GAMEN and Leu8OT).DiscussionThe coevolution of AAMEN and VAMEN with their corresponding OTs and OTRs suggests a functional relationship that could have contributed to specific reproductive and adaptive behaviors, including paternal care, social monogamy, and twin births, prominent traits in Cebidae species, such as marmosets and tamarins. Our findings underscore the coevolution of taxon‐specific amino acids among the three studied molecules, shedding light on the oxytocinergic system as an adaptive epistatic repertoire in primates.

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Fast Scan Cyclic Voltammetry to Assess Dopamine Function: From Circuits to Behavior

Clark

España

2022

Dopaminergic System Function and Dysfunction: Experimental Approaches

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Chronic modafinil administration to preadolescent rats impairs social play behavior and dopaminergic system

Cited by 7 publications

References 73 publications

Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels

Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels

From molecular variations to behavioral adaptations: Unveiling adaptive epistasis in primate oxytocin system

Fast Scan Cyclic Voltammetry to Assess Dopamine Function: From Circuits to Behavior

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