effects of ritalin use on a young brain?

[user3]

I was prescribed Ritalin from age 4-11. I was wondering if the seven year soak of dopamine has impaired my ability to enjoy other CNS stimulants to their full potential. I've taken 30mg Adderall IR and haven't felt much of anything, euphoria, concentration, and stimulation seemed unchanged from baseline, where most people get a notable raises in those categories, same was true with 40mg of Ritalin (crushed long acting capsule, insuffilated or swallowed). Coke doesn't seem to do as much for me as it does others, nor did my encounter (albeit a small dose, 4mg) of desoxypirpradrol. So could it have been the seven years of Ritalin use (I think I may've peaked at 10mg twice a day), individuality (everyone reacts differently), an act of God, or natural tolerance that has affected how CNS stimulants act on my brain.

 

[SpunkySkunk347]

10mg twice daily isnt that high of a dose,
but for 7 years it definitely could be possible that a permenant tolerance developed.

 

[Pimp Lazy]

Just on general practice I wouldn't try to "enjoy" any stims. Stims and amps are bad news. I would say if anything your brain probably is worse off in this department. See studies citing ADD-meds and addiction potential later in life. This leads me to believe your DA system is worse off than other people's. I was on ADD meds for about 2 years less than yourself. I find myself doing more poorly now than I was before I ever ate an ADD drug. Last one I took was Concerta in about 2000. Oh and no drugs seem to do as much for me as they do for other people. I'd like to think it's my masterful self control, but I think people with ADD/drug users in general are trying to correct some balance. You'll need more of something to offset the balance to the same degree as your normal peers.

 

[user3]

As stated in the Ritalin FAQ (which I should've checked in the first place) and confirmed here (dated, I know), cross tolerance does develop btwn CNS stimulants. I found this (again, dated), relating to long-term neurotransmitter influence; however, I'm not sure how credible the source is.

Mods: maybe Advanced Drug Discussion.

 

[user3]

Does anyone have access to this article?

 

[TheLoveBandit]

ANON to ADD, perhaps to OD if needed

 

[vecktor]

Does anyone have access to this article?

I think you do!!
if you register as guest you get access to JAMA from 1995 onwards but not the last 6 months.
https://subs.ama-assn.org/ama/exec/guest?url=http://jama.ama-assn.org/
hope that helps
V

 

[mind]

or use one of the login details from bugmenot.com


http://www.bugmenot.com/view/jama.ama-assn.org

 

[user3]

http://www.bluelight.ru/vb/showthread.php?t=316682

for anyone else interested


Article

 

[user3]

http://www.bluelight.ru/vb/showthread.php?t=316682

maybe this one will work

if not: this

or just access the data directly from JAMA

any other articles are more than welcome

 

[Adrenochrome]

what the fuck y does it say user3 with posts:n/a?

 

[sodiumglow]

what the fuck y does it say user3 with posts:n/a?

I believe it was due to the OP being posted in Anon.

 

[nuke]

Short-term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats.
Adriani W, Leo D, Guarino M, Natoli A, Di Consiglio E, De Angelis G, Traina E, Testai E, Perrone-Capano C, Laviola G.

Department of Cell Biology & Neurosciences, Behavioural Neuroscience Section, Istituto Superiore di Sanità, viale Regina Elena 299, I-00161 Roma, Italy. [email protected]

Exposure to methylphenidate (MPH) during adolescence is the elective therapy for attention deficit/hyperactivity disorder (ADHD) children, but raises major concerns for public health, due to possibly persistent neurobehavioral changes. Rats (30- to 44-days old) were administered MPH (2 mg/kg, i.p once daily) or saline (SAL). At the end of the treatment we collected plasma, testicular, liver, and brain (striatum) samples. The testes and liver were used to evaluate conventional reproductive and metabolic endpoints. Testes of MPH-exposed rats weighed more and contained an increased quantity of sperm, whereas testicular levels of testosterone (TST) were markedly decreased. The MPH treatment exerted an inductive effect on enzymatic activity of TST hydroxylases, resulting in increased hepatic TST catabolism. These findings suggest that subchronic MPH exposure in adolescent rats could have a trophic action on testis growth and a negative impact on TST metabolism. We have analyzed striatal gene expression profiles as a consequence of MPH exposure during adolescence, using microarray technology. More than 700 genes were upregulated in the striatum of MPH-treated rats (foldchange >1.5). A first group of genes were apparently involved in migration of immature neural/glial cells and/or growth of novel axons. These genes include matrix proteases (ADAM-1, MMP14), their inhibitors (TIMP-2, TIMP-3), the hyaluronan-mediated motility receptor (RHAMM), and growth factors (transforming growth factor-beta3 [TGF-beta3] and fibroblast growth factor 14 [FGF14]). A second group of genes were suggestive of active axonal myelination. These genes mediate survival of immature cells after contact with newly produced axonal matrix (laminin B1, collagens, integrin alpha 6) and stabilization of myelinating glia-axon contacts (RAB13, contactins 3 and 4). A third group indicated the appearance and/or upregulation of mature processes. The latter included genes for: K+ channels (TASK-1, TASK-5), intercellular junctions (connexin30), neurotransmitter receptors (adrenergic alpha 1B, kainate 2, serotonin 7, GABA-A), as well as major proteins responsible for their transport and/or anchoring (Homer 1, MAGUK MPP3, Shank2). All these genes were possibly involved in synaptic plasticity, namely the formation, maturation, and stabilization of new neural connections within the striatum. MPH treatment seems to potentiate synaptic plasticity, which is an age-dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults. Our observations suggest that adolescent MPH exposure causes only transient changes in reproductive and hormonal parameters, and a more enduring enhancement of neurobehavioral plasticity.

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

 

[Chaos Butterfly]

Another anon post merged in up that way ^^^

CB.

 

[ziddy]

MPH treatment seems to potentiate synaptic plasticity, which is an age-dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults.

Is that desirable or undesirable?

 

[nuke]

Mmm, possibly bad. For instance, it may possibly enable learning, but may also predispose an individual to addiction if the human model follows the rat model:

Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use.
Ferrario CR, Gorny G, Crombag HS, Li Y, Kolb B, Robinson TE.

Department of Psychology (Biopsychology) and Neuroscience Program, University of Michigan, Ann Arbor, MIichigan 48109-1109, USA.

BACKGROUND: Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction. METHODS: Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies. RESULTS: When re-exposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex). CONCLUSIONS: The transition from stable to escalated cocaine use, a hallmark of addiction, is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.

PMID: 16098484 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

So in the future, the crackbabies of the 80s which was oft wrote about but never happened may actually occur this decade through the drug companies insiduously feeding our children stimulants...

There's also this though:

Preadolescent methylphenidate versus cocaine treatment differ in the expression of cocaine-induced locomotor sensitization during adolescence and adulthood.
Guerriero RM, Hayes MM, Dhaliwal SK, Ren JQ, Kosofsky BE.

Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital-East, Charlestown, USA.

BACKGROUND: Methylphenidate (MPH), the most commonly prescribed medication for childhood attention-deficit/hyperactivity disorder (ADHD), shares chemical and mechanistic similarities to cocaine which has stimulated research to address the addiction liability following treatment. METHODS: Utilizing locomotor sensitization we examined the consequences of recurrent MPH versus cocaine treatment during preadolescence in altering cocaine-induced locomotor behavior in adolescent and adult mice. Black Swiss Webster mice were treated with MPH, cocaine, or saline during preadolescence. To test whether MPH pretreatment during preadolescence contributed to an altered sensitivity to cocaine during adolescence, these mice were treated with recurrent cocaine or saline during adolescence. All mice were challenged with cocaine as adults. RESULTS: Recurrent MPH treatment, unlike cocaine treatment in preadolescent mice, had no effect on locomotor sensitization to cocaine during adolescence or adulthood, as compared with saline controls. Furthermore, unlike cocaine, administration of MPH in adolescence did not augment the response to cocaine challenge. CONCLUSIONS: MPH treatment during preadolescence does not increase subsequent sensitivity to cocaine, whereas cocaine treatment does. Thus, MPH treatment during preadolescence does not appear to persistently induce long-term adaptations, which may underlie an enhanced liability for subsequent drug abuse.

PMID: 16780809 [PubMed - indexed for MEDLINE]

...that still doesn't mean they're sensitized to methylphenidate though, which the other study showed...

and this:

Enduring behavioral effects of early exposure to methylphenidate in rats.
Carlezon WA, Mague SD, Andersen SL.

Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.

BACKGROUND: Methylphenidate (MPH) is a stimulant prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulant drugs can cause enduring behavioral adaptations, including altered drug sensitivity, in laboratory animals. We examined how early developmental exposure to stimulants affects behavior in several rodent models. METHODS: Rats received MPH or cocaine during preadolescence (P20-35). Behavioral studies began during adulthood (P60). We compared how early exposure to MPH and cocaine affects sensitivity to the rewarding and aversive properties of cocaine using place conditioning. We also examined the effects of early exposure to MPH on depressive-like signs using the forced swim test, and habituation of spontaneous locomotion, within activity chambers. RESULTS: In place-conditioning tests, early exposure to MPH or cocaine each made moderate doses of cocaine aversive and high doses less rewarding. Early MPH exposure also caused depressive-like effects in the forced swim test, and it attenuated habituation to the activity chambers.CONCLUSIONS: Early exposure to MPH causes behavioral changes in rats that endure into adulthood. Some changes (reduced sensitivity to cocaine reward) may be beneficial, whereas others (increases in depressive-like signs, reduced habituation) may be detrimental. The effects of MPH on cocaine-related behaviors may be a general consequence of early stimulant exposure.

PMID: 14675796 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/sites/e...ez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Some more:

Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood.
Bolaños CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ.

Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.

BACKGROUND: Methylphenidate (MPH) is a psychomotor stimulant medication widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathways activated by drugs of abuse, most research has focused on assessing MPH's potential to alter an individual's risk for adult drug addiction. Data examining other potential long-term behavioral consequences of early MPH administration are lacking, however. METHODS: We investigated the long-term behavioral consequences of chronic administration of MPH (2.0 mg/kg) during pre- and periadolescent development in adult rats by assessing their behavioral reactivity to a variety of emotional stimuli. RESULTS: The MPH-treated animals were significantly less responsive to natural rewards such as sucrose, novelty-induced activity, and sex compared with vehicle-treated control animals. In contrast, MPH-treated animals were significantly more sensitive to stressful situations, showed increased anxiety-like behaviors, and had enhanced plasma levels of corticosterone. CONCLUSIONS: Chronic exposure to MPH during development leads to decreased sensitivity to rewarding stimuli and results in enhanced responsivity to aversive situations. These results highlight the need for further research to improve understanding of the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.

PMID: 14675795 [PubMed - indexed for MEDLINE]

Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis.
Lagace DC, Yee JK, Bolaños CA, Eisch AJ.

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

BACKGROUND: The neural consequences of early-life exposure to methylphenidate (MPH; Ritalin) are of great interest given the widespread, and sometimes inappropriate, use in children. Here we examine the impact of juvenile MPH exposure on adult hippocampal neurogenesis. METHODS: Rats received MPH (2.0 mg/kg, intraperitoneal, twice daily) or saline (SAL) during preadolescence (postnatal days 20-35). Hippocampal cell proliferation (Experiment 1), neurogenesis (Experiment 2), and stress-induced changes in cell proliferation (Experiment 3) were assessed at several developmental stages including adulthood. RESULTS: Juvenile exposure to MPH did not alter proliferation at any developmental time point relative to control rats; however, exposure to MPH significantly decreased the long-term survival of newborn cells in adult rats, particularly in the temporal hippocampus. Although MPH-treated rats had higher levels of corticosterone after restraint stress, they did not show the expected greater decrease in hippocampal cell proliferation relative to control animals. CONCLUSIONS: Early-life exposure to MPH inhibits the survival of adult-generated neurons in the temporal hippocampus and may reduce progenitor sensitivity to corticosterone-induced decreases in proliferation. These findings suggest that decreased adult neurogenesis is an enduring consequence of early-life exposure to MPH and are discussed for their relevance to humans.

PMID: 16893528 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/sites/e...med.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus

Wouldn't be surprised if there's lots more out there...

 

[ziddy]

Early-life exposure to MPH inhibits the survival of adult-generated neurons in the temporal hippocampus

Is this a result of acute administration, or chronic? In other words, is this likely to occur from occasional use (perhaps a dozen times per year) or will it only happen in response to daily use for months or years?

 

[pseudointellectual]

aren't most (if not all) of those IV admin? I'd like to see something on oral admin.

 

[nuke]

Is this a result of acute administration, or chronic? In other words, is this likely to occur from occasional use (perhaps a dozen times per year) or will it only happen in response to daily use for months or years?

It's likely to occur if administered at moderate doses by a syringe to rats during their child-like stage of life.

 

[ziddy]

So is 17-18 young enough to matter in this regard, or are such concerns more applicable to young children?