Miguel Patrícia Maidana, Bronauth Loise Peres, Deniz Bruna Ferrary, Confortim Heloisa Deola, de Oliveira Bruna Chaves, Dalle Molle Roberta, Silveira Patrícia Pelufo, Pereira Lenir Orlandi
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Ciências Morfológicas, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
Departamento de Ciências Morfológicas, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Exp Neurol. 2022 Jul;353:114071. doi: 10.1016/j.expneurol.2022.114071. Epub 2022 Apr 7.
Impulsivity, as observed in patients diagnosed with Attention-deficit/hyperactivity disorder (ADHD), can induce dysregulated behaviors such as binge eating and drug addiction. We previously demonstrated that neonatal hypoxia-ischemia (HI) resulted in ADHD-like behaviors in rats and that methylphenidate (MPH) administration (the first therapeutic option for ADHD) reversed these deficits. Here, we aimed at investigating addictive-like behaviors, such as the reward-based feeding behavior (using the BioDAQ monitor) and ethanol consumption (using the IA2BC procedure) in adult animals subjected to neonatal HI and treated with or without MPH. Male Wistar rats were divided into four groups (n = 10-12/group): control saline (CTS), CTMPH, HI saline (HIS) and HIMPH. The HI procedure was conducted at postnatal day (PND) 7 and behavioral analyses between PND 60-90, in which MPH (2.5 mg/kg, i.p.) was administered 30 min prior to each behavioral evaluation (6 sessions in BioDAQ and 12 sessions in the IA2BC protocol). HI animals had a dysregulated feeding intake shortly after eating a small piece of the palatable diet, and MPH reversed this dysregulated pattern. However, when the palatable diet was freely available, MPH stimulated a higher intake of this diet in the first exposure day, and this effect was potentialized in HIMPH rats. Increased ethanol intake was observed in HI rats, and MPH administration alleviated this behavior; contrarily, MPH treatment in control rats induced an increase in ethanol consumption. The present findings give additional support to the relationship between neonatal HI and ADHD but the differential response to MPH in control or HI animals highlights the importance of avoiding indiscriminate use of MPH by healthy individuals.
在被诊断患有注意力缺陷多动障碍（ADHD）的患者中观察到的冲动性，可诱发暴饮暴食和药物成瘾等行为失调。我们之前证明，新生大鼠缺氧缺血（HI）会导致类似ADHD的行为，而给予哌甲酯（MPH，ADHD的首选治疗药物）可逆转这些缺陷。在此，我们旨在研究成年期经历新生期HI且接受或未接受MPH治疗的动物的成瘾样行为，如基于奖赏的进食行为（使用BioDAQ监测仪）和乙醇消耗（使用IA2BC程序）。雄性Wistar大鼠分为四组（每组n = 10 - 12）：对照生理盐水组（CTS）、对照MPH组（CTMPH）、HI生理盐水组（HIS）和HI MPH组（HIMPH）。HI操作在出生后第7天（PND 7）进行，行为分析在PND 60 - 90之间进行，其中在每次行为评估前30分钟腹腔注射MPH（2.5 mg/kg）（BioDAQ实验6次，IA2BC实验12次）。HI动物在食用一小片美味食物后不久进食量失调，而MPH逆转了这种失调模式。然而，当美味食物可自由获取时，MPH在首次接触日刺激了对这种食物的更高摄入量，且这种效应在HIMPH大鼠中更明显。HI大鼠的乙醇摄入量增加，给予MPH可减轻这种行为；相反，对照大鼠接受MPH治疗会导致乙醇消耗增加。本研究结果进一步支持了新生期HI与ADHD之间的关系，但对照动物或HI动物对MPH的不同反应凸显了健康个体避免滥用MPH的重要性。
