Sensitization to locomotor effects of methylphenidate in the rat

Gaytan, Osvaldo; al-Rahim, Sarah; Swann, Alan C.; Dafny, Nachum

doi:10.1016/s0024-3205(97)00598-5

Cited by 107 publications

(83 citation statements)

References 8 publications

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“…A dose of 10 mg/kg MP produces more locomotor activity than higher or lower doses of the drug (Gaytan et al 1997;Crawford et al 1998;McDougall et al 1999), an effect observed in both young and older animals. We found that 2 weeks following repeated treatment with MP (10 mg/kg IP), a threshold challenge dose of cocaine (7.5 mg/kg IP) significantly enhanced ambulations and rearing, as compared to saline-treated animals.…”

Section: Cross Sensitization From Mp To Cocainementioning

confidence: 93%

Section: Treatment Of Attention Deficit Hyperactivity Disorder With Tmentioning

confidence: 99%

“…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%

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

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

225

147

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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...

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Section: Cross Sensitization From Mp To Cocainementioning

confidence: 93%

Section: Treatment Of Attention Deficit Hyperactivity Disorder With Tmentioning

confidence: 99%

mentioning

confidence: 99%

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

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

225

147

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“…The effects of repeated MPH administration have not been consistent, with behavioral sensitization reported by some (Gaytan, al‐Rahim, Swann, & Dafny, 1997; Kuczenski & Segal, 2001; Sripada, Gaytan, Al‐rahim, Swann, & Dafny, 1998) but not by other (Crawford, McDougall, Meier, Collins, & Watson, 1998; Izenwasser et al., 1999) studies. Most of these studies, however, employed a prolonged pretreatment or induction phase and were conducted in adult subjects only.…”

Section: Discussionmentioning

confidence: 84%

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats

et al. 2018

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IntroductionThere has been an increasing interest in analyzing the interactions between stimulants and ethanol during childhood and adolescence. Stimulants are used to treat attention‐deficit hyperactivity disorder (ADHD) in these developmental stages, during which ethanol initiation and escalation often occur.MethodsThis study assessed the effects of repeated d‐amphetamine (AMPH) or methylphenidate (MPH) treatment during adolescence [male and female Wistar rats, between postnatal day (PD) 28 to PD34, approximately] on the initiation of ethanol intake during a later section of adolescence (PD35 to PD40).ResultsAmphetamine and MPH exerted reliable acute motor stimulant effects, but there was no indication of sensitized motor or anxiety responses. MPH did not affect dopamine (DA) levels, whereas AMPH significantly reduced insular levels of DA in both sexes and norepinephrine levels in females only. Repeated treatment with AMPH, but not with MPH, enhanced ethanol intake during late adolescence in male, but not in female, rats.ConclusionA short treatment with AMPH during adolescence significantly altered DA levels in the insula, both in male and females, and significantly enhanced ethanol intake in males. The present results suggest that, in adolescent males, a very brief history of AMPH exposure can facilitate the initiation of ethanol intake.

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“…The comparison of activity on ED 11 post MPD exposure with the activity on ED 2 post initial MPD exposure was to determine the effect of MPD at the expression phase and find out whether behavioral sensitization was established [20] [23]. Since chronic MPD exposure can elicit behavioral sensitization [16] [18] [20] [24] [25]. The locomotor differences between ED 1 (baseline) and ED 12 (after ethanol administration) were used for ethanol control ( Table 1).…”

Section: Discussionmentioning

confidence: 99%

Ritalin Use Modifies Alcohol Effects in Rats

Sonne¹,

Dafny²

2014

JBBS

Self Cite

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Methylphenidate (MPD), known as Ritalin, is a common drug prescribed for those diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).There are reports that many MPD users consume alcohol, resulting in toxic effects and hospitalization. The goal of this study was to investigate the effects of ethanol in rats concomitant with acute and repetitive MPD exposure. Rats were divided into four groups, control (saline), 0.6 mg/kg MPD, 2.5 mg/kg MPD, and 10.0 mg/kg MPD groups and lasted for 12 consecutive days. Ethanol was given after repeated MPD administration as follows. On experimental day 1 (ED 1), all animals were treated with saline to establish baseline, on ED 2 through ED 7 either saline or MPD (0.6, 2.5, or 10.0 mg/kg) was given. On ED 11, after three days without treatment (ED 8 -10), rats were treated as they were on ED 2 -7. At ED 12, 1 g/kg ethanol was administered, and one hour of locomotor activity was recorded after alcohol administration, using the open field assay. The data show a dose response characteristic of increased locomotor activity with increasing doses of MPD. Ethanol administration alone depresses locomotor activity. The depressive effect of alcohol was significantly attenuated in animals treated with MPD, in a dose dependent manner. The higher dose of MPD previously administered resulted in a larger attenuation of the ethanol's suppressive effect. These trends demonstrate that chronic MPD exposure directly influences the effects of alcohol in rats. Under these circumstances, it is reasonable to assume that a subject will need to consume an increased amount of ethanol in order to attain the ethanol effect desired. This discrepancy between effects and exposure may be a liability for ethanol toxicity.

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Sensitization to locomotor effects of methylphenidate in the rat

Cited by 107 publications

References 8 publications

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

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

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats

Ritalin Use Modifies Alcohol Effects in Rats

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