Methylphenidate dose–response behavioral and neurophysiological study of the ventral tegmental area and nucleus accumbens in adolescent rats

• Published in: The European journal of neuroscience 2019-08, Vol.50 (4), p.2635-2652
• Main Authors: Broussard, Elzia, Reyes‐Vazquez, Cruz, Dafny, Nachum
• Format: Article
• Language: English
• Subjects: behavioral sensitization; behavioral tolerance; Cognitive ability; Dosage; Drug abuse; Drug dosages; Drug tolerance; Methylphenidate; Nucleus accumbens; Rodents; Stimulants; Teenagers; ventral tegmental area; Ventral tegmentum
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14402

The psychostimulant methylphenidate (MPD) is the most common medication used in treating ADHD in children. Studies have shown an increasing prevalence among adolescents without ADHD to take MPD as a cognitive booster and recreational drug, even though it is a Schedule II drug and has a high potential for abuse. The objective of this study is to explore if there is an association between the animals’ behavioral and neurophysiological responses to acute and/or chronic methylphenidate exposure within the ventral tegmental area and the nucleus accumbens, and to compare how these two brain structures fire in response to methylphenidate. Freely moving adolescent rats implanted with semimicroelectrodes within the VTA and NAc were divided into three MPD dosing groups: 0.6, 2.5, and 10 mg/kg i.p., as well as a saline control group. The animals were divided into two groups based on their behavioral responses to chronic MPD, behavioral sensitization and tolerance, and the neuronal responses of the two groups were compared for each MPD dosing. Significant differences in the proportion of neuronal units in the VTA and NAc responding to MPD were observed at the 0.6 and 10.0 mg/kg MPD dosing groups. Moreover, the same doses of 0.6, 2.5, and 10.0 mg/kg MPD elicited behavioral sensitization in some animals and behavioral tolerance in others. This specific study shows that the VTA and NAc neurons respond differently to the same doses of MPD. MPD has different neuronal and behavioral effects depending on the individual, the dosage of MPD, and the brain structure studied. Significant differences in the proportion of neuronal units in the VTA and NAc responding to MPD were observed at the 0.6 and 10.0 mg/kg MPD dosing groups. The same doses of 0.6, 2.5, and 10.0 mg/kg MPD elicited behavioral sensitization in some animals and tolerance in others. This study shows that the VTA and NAc neurons respond differently to the same doses of MPD. MPD has different neuronal and behavioral effects depending on the individual, the dosage of MPD, and the brain structure studied.