Methylphenidate alters basal ganglia neurotensin systems through dopaminergic mechanisms: a comparison with cocaine treatment

Alburges, Mario E.; Hoonakker, Amanda J.; Horner, Kristen A.; Fleckenstein, Annette E.; Hanson, Glen R.

doi:10.1111/j.1471-4159.2011.07215.x

Cited by 23 publications

(30 citation statements)

References 55 publications

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“…Alone, SCH 23390 had no significant effect on NTLI concentrations in any of the basal ganglia structures examined, whereas eticlopride increased the NTLI content in the anterior dorsal striatal region (P<0.05), but not in any other structure examined (Figs. 3 and 4) as previously reported with other D2 antagonists (Letter et al 1987a; Merchant et al 1988; Hanson et al 1989; Alburges and Hanson 1999; Alburges et al 2011). In general, blockade of the D2 receptor antagonized METH-induced reductions in all of basal ganglia structures (compare eticlopride-saline [E-S] vs. eticlopride-METH [E-M] groups).…”

Section: Resultssupporting

confidence: 77%

Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine

et al. 2014

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Rationale Administration of high doses of methamphetamine (METH) in a manner mimicking the bingeing patterns associated with abuse, reduces NT release and causes its accumulation and elevated NT levels in extrapyramidal structures by a D1 mechanism. The relevance of these findings to the therapeutic use of METH needs to be studied. Objectives The effect of low doses (comparable to that used for therapy) of METH on basal ganglia NT systems was examined and compared to high-dose and self-administration effects previously reported. Methods Rats were injected four times (2-h intervals) with either saline or low doses of METH (0.25, 0.50 or 1.00 mg/kg/s.c.). For the DA antagonist studies, animals were pretreated with a D1 (SCH23390) or D2 (eticlopride) antagonist 15 min prior to METH or saline treatments. Rats were sacrificed 5–48 h after last injection. Results METH at doses of 0.25 and 0.50, but not 1.00 mg/kg rapidly and briefly decreased NTLI concentration in all basal ganglia structures studied. In the posterior dorsal striatum, the reduction in NT level after low-dose METH appeared to be caused principally by D2 stimulation, but both D2 and D1 stimulation were required for the NT responses in the other basal ganglia regions. Conclusions A novel finding from the present study was that opposite to abuse-mimicking high doses of METH, the therapeutically relevant low-dose METH treatment reduced NT tissue levels likely reflecting an increase in NT release and a short-term depletion of the levels of this neuropeptide in basal ganglia structures. The possible significance is discussed.

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Section: Resultssupporting

confidence: 77%

Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine

et al. 2014

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“…Several reports state that psychostimulant exposure in some animals elicits CREB upregulation, while the same drug and dose in other animals elicits ΔFosB upregulation (Alburges et al, 2011; Brandon and Steiner, 2003; Nikolaus et al, 2011; Yano and Steiner, 2005). Direct correlations between upregulation of ΔFosB or CREB as a result of repetitive psychostimulant exposure were reported to correlate with the behavioral responses such as behavioral sensitization or tolerance, respectively (Chao and Nestler, 2004; Kim et al, 2009; Nestler, 2004; 2008).…”

Section: Discussionmentioning

confidence: 99%

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

Claussen

Dafny

2015

Pharmacology Biochemistry and Behavior

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The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0 mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization were also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals was observed for the 2.5 and 10.0 mg/kg MPD exposed groups. For 2.5 mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0 mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0 mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and oppositely at ED10 MPD rechallenge. While the behaviorally sensitized animals in general increased in their percentage change of firing rats were observed following acute 10.0 mg/kg MPD and the behaviorally sensitized 10.0 mg/kg MPD animals and a robust increase in neuronal firing rates at ED1 and ED10 rechallenge. These results suggest the need to first individually analyze animal behavioral activity, and than to evaluate the neuronal responses to the drug based on the animals behavioral response to chronic MPD exposure.

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“…Similar to other psychostimulants (Steiner & Van Waes 2013), methylphenidate-induced gene regulation in the striatum is mediated by dopamine receptor activation (Yano et al 2006; Alburges et al 2011). However, serotonin contributes to gene regulation by psychostimulants such as cocaine (e.g., Bhat & Baraban 1993; Lucas et al 1997; Horner et al 2005; Szucs et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The former include upregulated dynorphin signaling in the striatum, which has been demonstrated after repeated cocaine/amphetamine exposure in animal models as well as in human drug users (Steiner & Gerfen 1998; Shippenberg et al 2007). Dynorphin expression is also increased by methylphenidate (Brandon & Steiner 2003; Yano & Steiner 2005b; Alburges et al 2011), and this response is potentiated by fluoxetine (Van Waes et al 2012). Dynorphin acts, at least in part, as a negative feedback mechanism (Steiner & Gerfen 1998) to limit dopamine and glutamate input to striatal neurons, and, given that both neurotransmitters are critical for psychostimulant-induced gene expression, dynorphin may thereby limit gene induction (see Steiner & Van Waes 2013, for discussion).…”

Section: Discussionmentioning

confidence: 99%

Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a

et al. 2013

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There is a growing use of psychostimulants such as methylphenidate (Ritalin; dopamine reuptake inhibitor) for medical treatments and as cognitive enhancers in the healthy. Methylphenidate is known to produce some addiction-related gene regulation. Recent findings in animal models show that selective serotonin reuptake inhibitors (SSRIs) including fluoxetine can potentiate acute induction of gene expression by methylphenidate, thus indicating an acute facilitatory role for serotonin in dopamine-induced gene regulation. We investigated whether repeated exposure to fluoxetine in conjunction with methylphenidate in adolescent rats facilitated a gene regulation effect well-established for repeated exposure to illicit psychostimulants such as cocaine - blunting (repression) of gene inducibility. We measured, by in situ hybridization histochemistry, the effects of a 5-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or a combination on the inducibility (by cocaine) of neuroplasticity-related genes (Zif268, Homer1a) in the striatum. Repeated methylphenidate treatment alone produced minimal gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine added to methylphenidate robustly potentiated methylphenidate-induced blunting for both genes. This potentiation was widespread throughout the striatum, but was most robust in the lateral, sensorimotor striatum, thus mimicking cocaine effects. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs such as fluoxetine may increase the addiction liability of methylphenidate.

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Methylphenidate alters basal ganglia neurotensin systems through dopaminergic mechanisms: a comparison with cocaine treatment

Cited by 23 publications

References 55 publications

Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine

Responses of the rat basal ganglia neurotensin systems to low doses of methamphetamine

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a

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