Age and genetic strain differences in response to chronic methylphenidate administration

Peng, Yang; Cuellar, Derly O.; Swann, Alan C.; Dafny, Nachum

doi:10.1016/j.bbr.2010.11.034

Cited by 35 publications

(30 citation statements)

References 73 publications

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“…These results are not in accord with the conclusion reached by Dafny and colleagues that “the SHR group is the least susceptible to development of behavioral sensitization” [10]. Rather, our results suggest that SHR rats are more vulnerable than other strains to methylphenidate-induced cross-sensitization to the locomotor-activating effects of cocaine when methylphenidate is administered in an environment other than home.…”

Section: Resultscontrasting

confidence: 99%

Differential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function of strain in adolescent and young adult rats

Yetnikoff

Arvanitogiannis

2013

Behav Brain Funct

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BackgroundBehavioral effects of stimulant drugs are influenced by non-pharmacological factors, including genetic variability and age. We examined acute and sensitized locomotor effects of methylphenidate in adolescent and early adult male Sprague Dawley (SD), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats using a drug regimen that differentiates clearly between initial and enduring differences in drug responsiveness. We probed for strain and age differences in the sensitizing effects of methylphenidate using a cocaine challenge. Methylphenidate was administered to the rats in a non-home environment.FindingsStrain differences in sensitivity to single methylphenidate injections depend on age and change with continuing drug pretreatment. While SHR rats are more sensitive to methylphenidate relative to WKY regardless of age and pretreatment day, SHR rats become more sensitive to methylphenidate than SD rats towards the end of pretreatment during early adulthood. SD rats exhibit greater sensitivity to methylphenidate relative to the WKY group during adolescence, an effect that dissipates with continued drug pretreatment during adulthood. Remarkably, only SHR rats, regardless of age, exhibit methylphenidate-induced cross-sensitization to the behavioral effects of cocaine.ConclusionsOur findings suggest that SHR rats are more vulnerable than other strains to methylphenidate-induced cross-sensitization to cocaine, at least when methylphenidate is administered in a non-home environment. Given that SHR rats are typically used to model features of attention deficit hyperactivity disorder, these findings may have important implications for the treatment of this disorder with methylphenidate.

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Section: Resultscontrasting

confidence: 99%

Differential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function of strain in adolescent and young adult rats

Yetnikoff

Arvanitogiannis

2013

Behav Brain Funct

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“…Indeed, we saw results pointing to the same direction, suggesting that previous methylphenidate exposure enhances further reinstatement of previously extinguished drug-seeking behavior, at least in Wistar rats. Meanwhile, Yang et al (2011) demonstrated that rats chronically administered with methylphenidate (2.5 or 10 mg/kg, IP for 6 days) showed strain-dependent ambulatory response to methylphenidate rechallenge (i.e. after 3 days of washout).…”

Section: Discussionmentioning

confidence: 99%

“…The SHR exhibits good face, construct and predictive validity, displaying hyperactivity, impulsivity, novelty seeking and sustained attention deficits relative to the normotensive control strain, the WKY rats . In some studies, the SHR showed variable locomotor responses to methylphenidate and did not manifest behavioral (locomotor) sensitization or tolerance to repetitive treatment of the drug (Yang et al 2003(Yang et al , 2011. Meanwhile, the drug intake profile of the methylphenidatetreated SHR in the self-administration paradigm, considered as the most relevant animal model of drug addiction, has not yet been reported.…”

Section: Introductionmentioning

confidence: 93%

Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

et al. 2011

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The contrasting effects of repeated methylphenidate treatment in methylphenidate self-administration and reinstatement in Wistar and SHR, and the increased susceptibility of the Wistar rat strain to the reinforcing effects of methylphenidate indicate that "normal" individuals are more likely to develop psychological dependence to the drug and experience relapse. Meanwhile, the clinical use of methylphenidate may not produce drug dependence or relapse in ADHD patients.

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“…Previous dose response experiments using MPD from 0.1 to 40 mg/kg found that 2.5 mg/kg MPD (i.p.) elicited behavioral and neurophysiological sensitization ( Gaytan et al, 1996;Lee et al, 2009; Podet et al, 2010;Yang et al, 2001; 2003b; 2006a; 2006c; 2007; 2010; 2011). Thus, the 2.5 mg/kg MPD dose was used in this experiment.…”

Section: Methodsmentioning

confidence: 99%

Methylphenidate modulates the locus ceruleus neuronal activity in freely behaving rat

Tang

Dafny

2012

European Journal of Pharmacology

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The electrophysiological properties of the locus coeruleus (LC) neurons in response to acute and chronic administration of methylphenidate (MPD) were investigated. The extracellular LC neuronal activities were recorded from non-anesthetized, freely behaving rats previously implanted bilaterally with permanent semi microelectrodes. The main findings were: (1) On experimental day 1 (ED1), 87% (94/108) of LC units significantly changed their firing rate after initial (acute) MPD (2.5 mg/kg, i.p.) administration. The majority of the responsive units (80%, 75/94) increased their firing rate; (2) Daily MPD (2.5mg/kg) injection was given on ED2 through ED6 followed by 3 washout days (ED7 to 9). On ED10, all LC units exhibited a significant change of their baseline activity compared to their baseline activity on ED1; (3) MPD rechallenge on ED10 elicits 94% (101/108) of LC units significantly changed their firing rate; the majority of them (78%, 79/101) increased their firing rate; (4) The effect of rechallenge MPD administration on ED10 were compared to the effect of initial MPD on ED1, 98% of the LC units exhibited a significant change in their firing rate. 41% (43/106) of them exhibited a significant increase in their firing rate while 59% (63/106) units significantly decreased their firing rate which can be interpreted as electrophysiological sensitization or tolerance respectively. In conclusion, the majority of LC neurons significantly increased their firing rate after acute and chronic MPD administration. This data demonstrated that enhanced LC neuronal activities play important role in the effect of MPD.

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Age and genetic strain differences in response to chronic methylphenidate administration

Cited by 35 publications

References 73 publications

Differential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function of strain in adolescent and young adult rats

Differential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function of strain in adolescent and young adult rats

Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

Methylphenidate modulates the locus ceruleus neuronal activity in freely behaving rat

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