Age-related distribution of c-fos expression in the striatum of CD-1 mice after acute methylphenidate administration

Penner, Marsha R.; McFadyen, Melanie P.; Pinaud, Raphael; Carrey, Normand; Robertson, Harold A.; Brown, Richard E.

doi:10.1016/s0165-3806(02)00308-5

Cited by 40 publications

(25 citation statements)

References 50 publications

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“…We have shown, for instance, that a single acute injection of MPH induces age-dependent differential expression of the immediate early gene c-fos in the brains of CD-1 mice (Penner et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

McFadyen

Brown

Carrey³

2002

Developmental Psychobiology

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Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been conducted to determine its potential long-term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.).

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Section: Discussionmentioning

confidence: 99%

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

McFadyen

Brown

Carrey³

2002

Developmental Psychobiology

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“…Increased Fos protein levels were shown in different species for a range of doses and routes of administration (cat, 2.5 mg/kg, p.o. (Lin et al, 1996); mouse, 5 and 20 mg/kg, s.c. (Penner et al, 2002); 30 mg/kg, i.p. (Trinh et al, 2003); rat, 2-20 mg/kg, s.c. (Chase et al, 2003)).…”

Section: Methylphenidate Affects Transcription Factorsmentioning

confidence: 99%

“…Acute effects are often predictive of longterm molecular changes in terms of location and magnitude (eg Brandon and Steiner, 2003;Willuhn et al, 2003). Of the few studies that have examined effects of acute methylphenidate on striatal gene expression, most focused on c-fos induction (Lin et al, 1996;Acheson et al, 2001;Penner et al, 2002;Brandon and Steiner, 2003;Chase et al, 2003). Acute effects on the expression of neuropeptides in the striatum have so far not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Topography of Methylphenidate (Ritalin)-Induced Gene Regulation in the Striatum: Differential Effects on c-Fos, Substance P and Opioid Peptides

Yano

Steiner

2004

Neuropsychopharmacol

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Dopamine action alters gene regulation in striatal neurons. Methylphenidate increases extracellular levels of dopamine. We investigated the effects of acute methylphenidate treatment on gene expression in the striatum of adult rats. Molecular changes were mapped in 23 striatal sectors mostly defined by their predominant cortical inputs in order to determine the functional domains affected. Acute administration of 5 and 10 mg/kg (i.p.) of methylphenidate produced robust increases in the expression of the transcription factor c-fos and the neuropeptide substance P. Borderline effects were found with 2 mg/kg, but not with 0.5 mg/kg. For 5 mg/kg, c-fos mRNA levels peaked at 40 min and returned to baseline by 3 h after injection, while substance P mRNA levels peaked at 40-60 min and were back near control levels by 24 h. These molecular changes occurred in most sectors of the caudate-putamen, but were maximal in dorsal sectors that receive sensorimotor and medial agranular cortical inputs, on middle to caudal levels. In rostral and ventral striatal sectors, changes in c-fos and substance P expression were weaker or absent. No effects were seen in the nucleus accumbens, with the exception of c-fos induction in the lateral part of the shell. In contrast to c-fos and substance P, acute methylphenidate treatment had minimal effects on the opioid peptides dynorphin and enkephalin. These results demonstrate that acute methylphenidate alters the expression of c-fos and substance P preferentially in the sensorimotor striatum. These molecular changes are similar, but not identical, to those produced by other psychostimulants.

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“…Several works have evaluated toxic effects of MPH in the central nervous system and its relation with age and time of exposure to the drug (Volkow et al, 1998;Greenhill 2001;Yano and Steiner 2005;Grund et al, 2006;Chase et al, 2007;Gray et al, 2007;Yano and Steiner 2007). Some of these studies reported MPH effects in the central nervous system during childhood and adolescence exposure; its effects could be attributed to alterations in the dopaminergic circuits function (Brandon and Steiner 2003;Federici et al, 2005;Mague et al, 2005), gene expression (Penner et al, 2002;Chase et al, 2003Chase et al, , 2007Brandon and Steiner 2003) and others molecular changes related to neuronal metabolism (Fukui et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Methylphenidate increases creatine kinase activity in the brain of young and adult rats

Scaini¹,

Fagundes²,

Rezin³

et al. 2008

Life Sciences

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Age-related distribution of c-fos expression in the striatum of CD-1 mice after acute methylphenidate administration

Cited by 40 publications

References 50 publications

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

Topography of Methylphenidate (Ritalin)-Induced Gene Regulation in the Striatum: Differential Effects on c-Fos, Substance P and Opioid Peptides

Methylphenidate increases creatine kinase activity in the brain of young and adult rats

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