Acute and chronic methylphenidate administration in intact and VTA-specific and nonspecific lesioned rats
Methylphenidate (MPD) is a psychostimulant used for the treatment of ADHD and works by increasing the bioavailability of dopamine (DA) in the brain. As a major source of DA, the ventral tegmental area (VTA) served as the principal target in this study as we aimed to understand its role in modulating the acute and chronic MPD effect. Forty-eight male Sprague–Dawley rats were divided into control, sham, electrical lesion, and 6-OHDA lesion groups. Given the VTA’s implication in the locomotive circuit, three locomotor indices—horizontal activity, number of stereotypy, and total distance—were used to measure the animals’ behavioral response to the drug. Baseline recording was obtained on experimental day 1 (ED 1) followed by surgery on ED 2. After recovery, the behavioral recordings were resumed on ED 8. All groups received daily intraperitoneal injections of 2.5 mg/kg MPD for six days after which the animals received no treatment for 3 days. On ED 18, 2.5 mg/kg MPD was re-administered to assess for the chronic effect of the psychostimulant. Except for one index, there was an increase in locomotive activity in all experimental groups after surgery (in comparison to baseline activity), acute MPD exposure, induction with six daily doses, and after MPD re-challenge. Furthermore, the increase was greatest in the electrical VTA lesion group and lowest in the 6-OHDA VTA lesion group. In conclusion, the results of this study suggest that the VTA may not be the primary nucleus of MPD action, and the VTA plays an inhibitory role in the locomotive circuit.
KeywordsBehavior Locomotion Ritalin CNS lesion Psychostimulant Sensitization
The study was supported by NIH RO1 DA 02722 Grant.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
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