A comparison of the motor-activating effects of acute and chronic exposure to amphetamine and methylphenidate

McNamara, C.; Davidson, Emily S.; Schenk, Susan

doi:10.1016/0091-3057(93)90532-x

Cited by 63 publications

(50 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the determination of a dose-response curve is critical for ascertaining the differential effects of MPH on more complex behaviors in mice, most particularly at lower doses, which are more clinically relevant. Furthermore, in situations of repeated administration, the overall stimulatory effects of MPH are controversial, with some studies demonstrating increased spontaneous locomotion or stereotypy (Crawford, McDougall, Meier, Collins, & Watson, 1998;Gaytan, Al-Rahim, Swann, & Dafny 1997;Kuczenski & Segal, 2001;Sripada, Gaytan, Al-Rahim, Swann, & Dafny, 1998) while others show no such increase (Crawford et al, 1998;Izenwasser et al, 1999;McNamara, Davidson, & Schenk, 1993).…”

Section: Introductionmentioning

confidence: 96%

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

McFadyen

Brown

Carrey³

2002

Developmental Psychobiology

View full text Add to dashboard Cite

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.).

show abstract

Section: Introductionmentioning

confidence: 96%

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

McFadyen

Brown

Carrey³

2002

Developmental Psychobiology

View full text Add to dashboard Cite

show abstract

“…The low-dose requirement is due to the reversal of depolarization inactivation that is mediated by hyperpolarization of VTA DA neurons with the activation somatodendritic DA autoreceptors, which are far more sensitive than the postsynaptic DA receptors in DA terminal areas (Chiodo, 1988). In control animals, this dose of methylphenidate does not lead to behavioral activation (McNamara et al, 1993), perhaps due to a lack of effect on the activity of DA neurons and extracellular DA levels in the terminal areas to activate postsynaptic DA receptors (Kuczenski and Segal, 2002). These results are consistent with the low-dose requirement of stimulants in treating attention deficit/hyperactivity disorder (ADHD) and may explain why, at least in some ADHD cases (Sachdev and Trollor, 2000), doses of methylphenidate insufficient for behavioral activation can treat attention problems.…”

Section: Downloaded Frommentioning

confidence: 99%

Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission

Choong¹,

Shen²

2004

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Altered neurotransmission in the mesolimbic dopamine (DA) system has been suggested to be the underlying cause of attention problems commonly observed in children with fetal alcohol spectrum disorder (FASD). Methylphenidate is effective in treating attention problems in children with FASD. However, the underlying mechanism is currently unknown. We have shown previously that reduced ventral tegmental area (VTA) DA neuron activity in prenatal ethanol-exposed animals can be normalized by DA agonist treatment. In the present study, we investigated the possibility that similar mechanism mediates the effect of methylphenidate using the in vivo extracellular single-unit recording technique in anesthetized animals. We observed that reduced VTA DA neuron activity in prenatal ethanol-exposed animals was normalized by methylphenidate. The effect of methylphenidate was mediated by increased extracellular levels of DA instead of norepinephrine because this effect was not altered by the coadministration of prazosin, an ␣ 1 receptor antagonist, and was mimicked by the application of DA transporter blockers, nomifensine and 1-2(-[bis(4-flurophenyl)methoxy]ethyl)-4-(3-phenyl)piperazine dihydrochloride (GBR 12909). These observations support our hypothesis that depolarization inactivation is the cause of prenatal ethanol exposure-induced reduction in VTA DA neuron activity. We speculate that methylphenidate normalized the activity of VTA DA neurons by increasing extracellular DA levels in the VTA and the activation of somatodendritic DA autoreceptors. As a result, the depolarization inactivation was removed by hyperpolarization. The normalized VTA DA neuron activity in prenatal ethanol-exposed animals may contribute to a restoration of DA neurotransmission and the therapeutic effect of methylphenidate in attention problems in children with FASD.Prenatal ethanol exposure leads to abnormalities in the function of the midbrain dopamine (DA) system. For example, there is a reduction in DA uptake and receptor binding sites, DA content, and the DA metabolites in both the somatodendritic and terminal areas (Rathbun and Druse, 1985;Cooper and Rudeen, 1988;Druse et al., 1990) in prenatal ethanol-exposed animals. Prenatal ethanol exposure also can lead to changes in DA neuron morphology [e.g., smaller cell bodies and retarded dendritic growth in DA neurons (Shetty et al., 1993), DA receptor function (Shen et al., 1995;Wang and Shen, 2002), and DA receptor-mediated behavior (Hannigan and Randall, 1996)]. Recently, impairment in sustained attention, which could be modulated by DA (Davids et al., 2003), was also reported in prenatal ethanol-exposed animals (Hausknecht et al., 2003).In previous electrophysiological studies, we have demonstrated that prenatal ethanol exposure leads to a persistent reduction in the electrical activity of the midbrain DA neurons without a loss of DA neurons (Shen et al., 1999;Xu and Shen, 2001). Because the electrical activity controls the synthesis and release of DA (Gonon and Buda, 1985; SuaudChagny et ...

show abstract

“…Unfortunately, animal studies have provided conflicting answers (Laviola et al 1995;Ujike et al 1995;Snyder et al 1998;Wood et al 1998;Izenwasser et al 1999;McDougall et al 1999;Zavala et al 2000). Sensitization to MP in rodent models has been well documented (Shuster et al 1982;Gaytan et al 1997;Crawford et al 1998; but see McNamara et al 1993), but the use of relatively high doses in most studies, and the apparent inability of MP to induce long-term locomotor sensitization in young animals (McDougall et al 1999), has raised questions regarding the clinical relevance of such findings (National Institute of Mental Health 1999).Animal studies have also shown that repeated exposure to psychostimulants increases the likelihood that rats will acquire drug self-administration (SA) with shorter latencies (Horger et al 1992) and at lower doses (Horger et al 1990), perhaps a more relevant display of sensitization as it relates to addiction. Pretreatment with such stimulants as nicotine, caffeine, and amphetamine produces enduring enhancements in the acquisition of cocaine SA (Valdez and Schenk 1994;Schenk and Davidson 1998).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

225

147

View full text Add to dashboard Cite

Treatment of attention deficit hyperactivity disorder with the psychostimulant drug methylphenidate (MP) has increased dramatically among schoolchildren. We tested whether repeated exposure to moderate doses of MP (5 and 10 mg/kg IP for 5 or 7 days) in adolescent rats increased reactivity to cocaine measured by motor responses (ambulations and rearing) to a cocaine challenge in adulthood. We later tested whether repeated exposure to a low dose of MP (2 mg/kg IP for 7 days) enhanced the psychomotor effects of cocaine, measured by different challenge doses (0-30 mg/kg) as well as to the reinforcing effects of cocaine, measured by self-administration of lowdose infusion (75 g/kg, IV). We found that exposure to moderate doses of MP enhanced psychomotor responses to cocaine but exposure to a low dose only increased cocaine self-administration. These results suggest that adolescent exposure to low doses of MP in rats mayMethylphenidate (Ritalin ® ) is used widely in the treatment of attention deficit hyperactivity disorder (ADHD), the most commonly diagnosed disorder of childhood (Swanson et al. 1998). During the 1990s, diagnosis and treatment of this disorder grew dramatically in the United States. Estimates show that up to 15% of school age children may be affected in certain geographical locations (Scahill and Schwab-Stone 2000) and that prevalence is estimated to be 5-10% in the general population (Swanson et al. 1998). In addition, preschoolers (Zito et al. 2000) and children who do not meet the diagnostic criteria for ADHD (Marshall 2000) have recently been identified as two new groups increasingly exposed to this drug. The duration of treatment is several years in childhood, more often extending into adolescence and adulthood (Garland 1998;Robin 1999;Silver 2000;Spencer et al. 2000).Animal studies have shown that MP is a psychostimulant, which, as with cocaine, blocks the dopamine transporter (DAT) (Kuczenski and Segal 1997); thereby increasing extracellular dopamine (DA) levels in the striatum and nucleus accumbens (Kuczenski 1983), brain regions involved in the locomotor and reinforcing effects of psychostimulants and other drugs of abuse (Koob and Bloom 1988 NO . 5 et al. 1999). Oral therapeutic doses of MP effectively block more than 50% of DATs (Volkow et al. 1998); thereby increasing extracellular DA levels (Volkow et al. 2001). These actions are highly associated with the reinforcing properties of drugs (Ritz et al. 1987). Taken together, the well-documented abuse potential of psychostimulants (for reviews see White and Wolf 1991;Robinson and Berridge 1993;Self and Nestler 1995), studies linking ADHD with subsequent substance abuse (Wilens et al. 1997;Clure et al. 1999;Schubiner et al. 2000), and the dearth of controlled studies on the effects of long-term stimulant exposure on the brain, all make MP exposure an important public health issue.Animal models of drug addiction clearly indicate that repeated exposure to psychostimulants results in augmented behaviors (sensitization) that can be detected lo...

show abstract

A comparison of the motor-activating effects of acute and chronic exposure to amphetamine and methylphenidate

Cited by 63 publications

References 17 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

Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission

Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

Contact Info

Product

Resources

About