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

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2020-11

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Universidad de Valparaíso

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Programa de Doctorado en Ciencias con mencion en Neurocienciass

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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.

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NEUROCIENCIA CONDUCTUAL, DOPAMINA, NEUROTRANSMISORES

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