Chronic methylphenidate treatment enhances water maze performance following traumatic brain injury in rats

Kline, Anthony E.; Yan, Hong; Bao, Juliang; Marion, Donald W.; Dixon, C. Edward

doi:10.1016/s0304-3940(00)00797-7

Cited by 103 publications

(83 citation statements)

References 19 publications

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“…Previous reports by our group show improvements in spatial learning with the chronic administration of MPH after moderate CCI [14]. The results of our study support previous studies by showing significant effects of MPH across all treated groups in latency to find the hidden platform over the course of acquisition trial testing and increases in time spent searching in the target quadrant for the platform during the probe trial for injured groups.…”

Section: Discussionsupporting

confidence: 90%

“…This task has been used in the past to detect improvements in spatial learning with chronic interventions after CCI [13,14,37]. Each animal underwent five days of acquisition trials.…”

Section: Morris Water Maze Testingmentioning

confidence: 99%

“…However in vivo electrochemical monitoring after CCI suggests that striatal DA neurotransmission remains impaired [38]. Moreover, several behavioral studies suggest functional hypodopaminergia after experimental TBI with controlled cortical impact (CCI) by reporting that daily administration of DA receptor agonists including methylphenidate (MPH) [14], bromocriptine [13], and amantadine [6] improve spatial learning in the Morris Water Maze (MWM).…”

Section: Introductionmentioning

confidence: 99%

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Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury

Wagner

Kline

Ren

et al. 2007

Behavioural Brain Research

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Evidence suggests that dopamine (DA) agonists improve cognition after traumatic brain injury (TBI). Methylphenidate (MPH) is a DA agonist that blocks the dopamine transporter (DAT). Moreover, female sex hormones modulate DAT expression. Therefore, the purpose of this study was to evaluate how MPH affects behavioral performance in male and female rats. Under anesthesia, rats underwent either controlled cortical impact (CCI) or sham injury operations. Beginning post-operative day one, rats received daily intraperitoneal injections of MPH (5mg/kg) or saline. Beam balance (BB) and beam walking (BW) were assessed on postoperative days 1-5. Exploratory behavior was assessed using an open field free choice novelty (FCN) task on day 13. Spatial memory was assessed with a Morris water maze (MWM) task on days 14-20. Multivariate analyses showed TBI females performed better than TBI males on both motor tasks (P<0.05 both comparisons), and MPH improved BB performance for both male and female injury groups (P=0.05) compared to their respective vehicle treated injury groups. Multivariate analysis showed that MPH enhanced MWM performance (spatial learning and retention) after TBI. Significant improvements were noted in injured males treated with MPH compared to their vehicle control (P<0.05) with respect to improvements in memory acquisition and retention. Further, injured females treated with MPH had faster swimming speeds than all other groups (P<0.05 all comparisons), and MPH increased activity in TBI females but not males in the FCN task (P<0.05). These results suggest that MPH is beneficial after TBI. However there are gender specific drug differences in behavioral performance and sensitivity to treatment with MPH that may have implications for treatment efficacy and dosing clinically after TBI.

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Section: Discussionsupporting

confidence: 90%

“…This task has been used in the past to detect improvements in spatial learning with chronic interventions after CCI [13,14,37]. Each animal underwent five days of acquisition trials.…”

Section: Morris Water Maze Testingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury

Wagner

Kline

Ren

et al. 2007

Behavioural Brain Research

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“…[1][2][3] These deficits include declarative memory and working memory dysfunction that are caused by damage to the hippocampus. [4][5][6][7][8][9][10][11] Problems with memory can interfere with post-TBI recovery, rehabilitation, and living an independent life. Both clinical and experimental studies have shown that hippocampal neurons are particularly vulnerable to TBI, and loss of these neurons can continue for weeks to months after moderate-to-severe TBI.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Eukaryotic Initiation Factor 2 Alpha Phosphatase Reduces Tissue Damage and Improves Learning and Memory after Experimental Traumatic Brain Injury

Dash

Hylin

Hood

et al. 2015

Journal of Neurotrauma

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Patients who survive traumatic brain injury (TBI) are often faced with persistent memory deficits. The hippocampus, a structure critical for learning and memory, is vulnerable to TBI and its dysfunction has been linked to memory impairments. Protein kinase RNA-like ER kinase regulates protein synthesis (by phosphorylation of eukaryotic initiation factor 2 alpha [eIF2a]) in response to endoplasmic reticulum (ER) stressors, such as increases in calcium levels, oxidative damage, and energy/glucose depletion, all of which have been implicated in TBI pathophysiology. Exposure of cells to guanabenz has been shown to increase eIF2a phosphorylation and reduce ER stress. Using a rodent model of TBI, we present experimental results that indicate that postinjury administration of 5.0 mg/kg of guanabenz reduced cortical contusion volume and decreased hippocampal cell damage. Moreover, guanabenz treatment attenuated TBI-associated motor, vestibulomotor, recognition memory, and spatial learning and memory dysfunction. Interestingly, when the initiation of treatment was delayed by 24 h, or the dose reduced to 0.5 mg/kg, some of these beneficial effects were still observed. Taken together, these findings further support the involvement of ER stress signaling in TBI pathophysiology and indicate that guanabenz may have translational utility.

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“…In addition, drugs causing central NE release induce recovery similar to AMPH (Sutton and Feeney, 1992;Goldstein, 1993), and drugs that interfere with NE release or synaptic transmission can retard recovery or reinstate deficits in recovered animals (Feeney and Westerberg, 1990;Goldstein and Davis, 1990;Dunn-Meynell et al, 1997). In addition to AMPH, multiple treatments with methylphenidate (Kline et al, 2000), a D2 receptor agonist (Kline et al, 2002) or a 5-HT(1A) receptor agonist (Kline et al, 2004) are reported to improve outcome after experimental TBI. More recently, chronic intermittent vagus nerve stimulation, which increases NE release (Roosevelt et al, 2006) and BDNF mRNA levels (Follesa et al, 2007) in cortex and hippocampus, has been shown to improve outcome after experimental TBI (Smith et al, 2005Clough et al, 2007).…”

mentioning

confidence: 99%

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

et al. 2008

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Prior work has shown that d-amphetamine (AMPH) treatment or voluntary exercise improves cognitive functions after traumatic brain injury (TBI). In addition, voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF). The current study was conducted to determine how AMPH and exercise treatments, either alone or in combination, affect molecular events that may underlie recovery following controlled cortical impact (CCI) injury in rats. We also determined if these treatments reduced injury-induced oxidative stress. Following a CCI or sham injury, rats received AMPH (1 mg/kg/day) or saline treatment via an ALZET ® pump and were housed with or without access to a running wheel for 7 days. CCI rats ran significantly less than sham controls, but exercise level was not altered by drug treatment. On day 7 the hippocampus ipsilateral to injury was harvested and BDNF, synapsin I and phosphorylated (P) -synapsin I proteins were quantified. Exercise or AMPH alone significantly increased BDNF protein in sham and CCI rats, but this effect was lost with the combined treatment. In sham-injured rats synapsin I increased significantly after AMPH or exercise, but did not increase after combined treatment. Synapsin levels, including the Psynapsin/total synapsin ratio, were reduced from sham controls in the saline-treated CCI groups, with or without exercise. AMPH treatment significantly increased the P-synapsin/total synapsin ratio after CCI, an effect that was attenuated by combining AMPH with exercise. Exercise or AMPH treatment alone significantly decreased hippocampal carbonyl groups on oxidized proteins in the CCI rats, compared with saline-treated sedentary counterparts, but this reduction in a marker of oxidative stress was not found with the combination of exercise and AMPH treatment. These results indicate that, whereas exercise or AMPH treatment alone may induce plasticity and reduce oxidative stress after TBI, combining these treatments may cancel each other's therapeutic effects. Keywordscontrolled cortical impact; norepinephrine; oxidized proteins; running wheel; traumatic brain injury *Corresponding author. Tel: +1-310-825-1904; fax: +1-310-794-2147. E-mail address: ggriesbach@mednet.ucla.edu (G. S. Griesbach). 1 G.S.G. and R.L.S. contributed equally to this work. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 June 27. Published in final edited form as:Neuroscience. 2008 June 23; 154(2): 530-540. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTraumatic brain injury (TBI) continues to be one of the leading causes of mortality and morbidity, with approximately 5.3 million Americans suffering from enduring disabilities resulting from TBI (Binder et al., 2005). Despite many experimental and clinical efforts using numerous therapeutic approaches, there are currently no proven treatments to alleviate the sequelae of TBI or to enhance recovery of function.Our laboratories have been investigating treatment strategies that may faci...

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Chronic methylphenidate treatment enhances water maze performance following traumatic brain injury in rats

Cited by 103 publications

References 19 publications

Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury

Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury

Inhibition of Eukaryotic Initiation Factor 2 Alpha Phosphatase Reduces Tissue Damage and Improves Learning and Memory after Experimental Traumatic Brain Injury

Voluntary exercise or amphetamine treatment, but not the combination, increases hippocampal brain-derived neurotrophic factor and synapsin I following cortical contusion injury in rats

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