Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders. Interestingly, children with ADHD seem to experience more ophthalmologic abnormalities, and the impact of methylphenidate (MPH) use on retinal physiology remains unclear. Thus, we aimed to unravel the retina’s structural, functional, and cellular alterations and the impact of MPH in ADHD versus the control conditions. For that, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used as animal models of ADHD and the controls, respectively. Animals were divided into four experimental groups as follows: WKY vehicle (Veh; tap water), WKY MPH (1.5 mg/kg/day), SHR Veh, SHR MPH. Individual administration was performed by gavage between P28-P55. Retinal physiology and structure were evaluated at P56 followed by tissue collection and analysis. The ADHD animal model presents the retinal structural, functional, and neuronal deficits, as well as the microglial reactivity, astrogliosis, blood-retinal barrier (BRB) hyperpermeability and a pro-inflammatory status. In this model, MPH had a beneficial effect on reducing microgliosis, BRB dysfunction, and inflammatory response, but did not correct the neuronal and functional alterations in the retina. Curiously, in the control animals, MPH showed an opposite effect since it impaired the retinal function, neuronal cells, and BRB integrity, and also promoted both microglia reactivity and upregulation of pro-inflammatory mediators. This study unveils the retinal alterations in ADHD and the opposite effects induced by MPH in the retina of ADHD and the control animal models.

The aim of this study was to evaluate whether paternal exposure to bupropion hydrochloride (BUP), an inhibitor of dopamine and noradrenaline reuptake, would affect the postnatal development of offspring. Male mice were divided into a BUP-treated (40mgkg−1day−1 by gavage, 45 days) or control (saline by gavage, 45 days) group (n=20 in each group). From Day 35 to Day 45 of treatment, males were allowed to mate with drug-naïve female mice. Postnatal development of the offspring (both sexes) was evaluated from Postnatal day (PND) 1 to PND60. Physical development parameters (weight gain, body length, incisor eruption, pinna detachment), anogenital distance, vaginal opening, reflexes (palmar grasp, surface righting, negative geotaxis and adult gait) and some behavioural parameters (locomotor activity and anxiety-like behaviour) were altered in the offspring of BUP-treated males. The results demonstrate that paternal exposure to BUP induces long-lasting changes in the postnatal development of the offspring.

Bupropion hydrochloride (BUP) has been associated with male sexual dysfunction. The aim of this study was to evaluate the effects of BUP on the reproductive function of male mice and to evaluate offspring development. The mice were distributed into BUP group (40 mg kg−1) and control group (saline). On Day 35 of treatment the males were placed to mate with females and then killed on Day 46 for evaluation of reproductive function. On Day 18 of pregnancy, pregnant females were killed for evaluation of congenital malformations in the offspring. The BUP group showed a decrease in the Johnsen score (Control, 9.354 ± 0.092; BUP, 7.615 ± 0.147), Sertoli (Control, 5.623 ± 0.184; BUP, 4.215 ± 0.097) and Leydig (Control, 11.430 ± 0.817; BUP, 7.531 ± 0.213) cell counts, testosterone levels (Control, 783.5 ± 154.2 ng dL−1; BUP, 201.4 ± 54.8 ng dL−1) and sperm production (Control, 2.852 ± 0.211; BUP, 1.988 ± 0.116) and increased morphological alterations of the sperm head (Control, 8.134%; BUP, 10.423%) and tail (Control, 4.96%; BUP, 16.211%). The congenital malformations observed in BUP-derived offspring were: kyphosis (Control, 0.00%; BUP, 5.26%), retroverted rear legs (Control, 14.43%; BUP, 53.68%), incomplete ossification of the supraoccipital and exoccipital (Control, 21.82%; BUP, 86.00%) and sternum (Control, 25.45%; BUP, 82.00%). BUP had toxic effects on testicular function and teratogenic potential.

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Nicotinamide participates in post transcriptional activities related to the maintenance of the original structure of the DNA. The chemotherapeutic agent cyclophosphamide induces severe chromosomal abnormalities in newborns. Thus, we investigated the possible protective effects of nicotine on the toxic and teratogenic model induced by cyclophosphamide. Pregnant mice were divided into experimental groups 1 and 2 (nicotinamide 100mg/ kg and 200mg/kg respectively); Experimental Group 3 (saline); Experimental group 4 (cyclophosphamide 50 mg/kg); Associated Treaty 5 and 6 (nicotinamide 100mg/kg and 200mg/kg associated with cyclophosphamide 50 mg/kg respectively). The results indicated that the exposure to nicotinamide in two doses, did not show any parameter of toxicity. We found that associated treatments 5 and 6 have been unable to minimize the adverse effects induced by cyclophosphamide on maternal toxicity and congenital malformations. However, the group associated with nicotinamide at a dose of 200mg/kg showed a protective effect on the increase in reabsorption rate, and nicotinamide in the two tested doses showed protective effects on decreased fetal and placental weight induced by cyclophosphamide. The results of this study showed that nicotinamide in a dose-dependent manner exerted protective effect and reduced the number of abortions and that the morbidity and mortality induced by cyclophosphamide was also reduced due to the nicotinamide.