Effects of Chronic Administration of Methylphenidate
August 18, 2015 at 12:06 AM | categories: mph
Contents
1 Chronic Actions of MPH
Although the acute effects methylphenidate (MPH) on human and animal behavior have been heavily studied, fewer studies have looked at longer-term effects and the consequences of long-term stimulant medication on the development of the adolescent brain is poorly understood [1]. With stimulant prescriptions to children and adolescents tripling during the 1990s, and seeing continued increases since then, there is a continued need to better understand the effects of MPH [1, 4, 7]. Clear reductions in symptoms justify treatment with stimulant medications [3], and in addition, untreated attention-deficit/hyperactivity disorder (ADHD) adolescents were at a 2-fold higher risk of developing drug abuse than medication-treated peers [10]; however, the long-term cognitive effects are less clear.
Long-term dopamine (DA) agonists often reduce the density of D2 receptors [6], and increase dopamine transporter (DAT) density [9], however, the effects of MPH and other stimulants on the density of DAT and D2 receptors depends on the experimental conditions used [7]. Despite the different ways in which drugs of abuse can affect DAT function, acute and long-term changes in the amount of the DAT at the cell surface emerge as a crucial mechanism in the chronic effects of drugs of abuse [11].
Pretreatment of rats with MPH (4 mg/kg i.p. bi-daily for four days) increases [3H]DA uptake and vesicular monamine transporter 2 (VMAT-2) levels in rat striatal vesicles ex vivo [5]. After 21 day treatment with 3 mg/kg MPH i.p., striatal DAT and basal DA levels were lower than saline treated spontaneously hypertensive rats (SHRs), an animal model of ADHD, however, K+-induced release and amphetamine (AMPH)-challenge induced higher DA release in the MPH treated rats [8]. In contrast, subcutaneous injection of adolescent mice for seven days with MPH (2.5 mg/kg to 80 mg/kg) did not show long-term behavioral effects, with no change in performance in open field, elevated plus maze or spatial learning paradigms [2].
Acronyms
- ADHD
- attention-deficit/hyperactivity disorder
- AMPH
- amphetamine
- DAT
- dopamine transporter
- DA
- dopamine
- MPH
- methylphenidate
- MTA
- The Multimodal Treatment Study of Children with ADHD Cooperative Group
- SHR
- spontaneously hypertensive rat
- VMAT-2
- vesicular monamine transporter 2
References
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