Effects of amphetamine, methylphenidate, and apomorphine on regional brain serotonin and 5-hydroxyindole acetic acid

Kuczenski, Ronald; Segal, David S.; Leith, Nancy J.; Applegate, Craig D.

doi:10.1007/bf00187252

Cited by 41 publications

(20 citation statements)

References 39 publications

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“…5B). Similar effects of amphetamine (13,60) and methylphenidate (59, 65) on c-Fos expression (59,60) and neurochemical indices of serotonergic transmission (13,65) in the frontal cortex of rats have been reported. The present data suggest that one of the potential mechanisms of psychostimulant action to affect glutamatergic transmission, and, consequently, dopaminergic hyperactivity, may involve modulation of 5-HT transmission in the frontal cortex.…”

Section: Psychostimulants Modulate Serotonergic Transmission In the Fsupporting

confidence: 61%

Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter

Gainetdinov

Mohn

Bohn

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

153

109

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In the brain, dopamine exerts an important modulatory influence over behaviors such as emotion, cognition, and affect as well as mechanisms of reward and the control of locomotion. The dopamine transporter (DAT), which reuptakes the released neurotransmitter into presynaptic terminals, is a major determinant of the intensity and duration of the dopaminergic signal. Knockout mice lacking the dopamine transporter (DAT-KO mice) display marked changes in dopamine homeostasis that result in elevated dopaminergic tone and pronounced locomotor hyperactivity. A feature of DAT-KO mice is that their hyperactivity can be inhibited by psychostimulants and serotonergic drugs. The pharmacological effect of these drugs occurs without any observable changes in dopaminergic parameters, suggesting that other neurotransmitter systems in addition to dopamine might contribute to the control of locomotion in these mice. We report here that the hyperactivity of DAT-KO mice can be markedly further enhanced when N-methyl-D-aspartate receptor-mediated glutamatergic transmission is blocked. Conversely, drugs that enhance glutamatergic transmission, such as positive modulators of L-␣-amino-3-hydroxy-5-methylisoxazole-4-propionate glutamate receptors, suppress the hyperactivity of DAT-KO mice. Interestingly, blockade of Nmethyl-D-aspartate receptors prevented the inhibitory effects of both psychostimulant and serotonergic drugs on hyperactivity. These findings support the concept of a reciprocal functional interaction between dopamine and glutamate in the basal ganglia and suggest that agents modulating glutamatergic transmission may represent an approach to manage conditions associated with dopaminergic dysfunction. F rontostriatal circuitry is one of the most prominent brain pathways involved in the control of locomotion, affect, impulsivity, attention, and emotion (1, 2). One axis of this circuitry involves dopaminergic projections into the striatal and mesolimbic brain areas (1, 3). Dopaminergic transmission has been intensively studied and is relatively well characterized (1, 3), largely because alterations in dopaminergic tone have clear behavioral manifestations such as changes in locomotor activity. In addition to dopaminergic innervation from substantia nigra and ventral tegmental area, the basal ganglia receive dense glutamatergic input predominantly from prefrontal cortical areas, as well as from the hippocampus, periventricular thalamus, and amygdala (1, 4, 5). There is a growing appreciation for the concept that dopaminergic and glutamatergic systems intimately interact at the level of medium-sized spiny neurons in the basal ganglia to control behavior (1, 6, 7). Particularly, an interaction at the levels of receptor signaling and regulation between dopamine D1 and͞or D2-like receptors and ionotropic glutamate N-methyl-D-aspartate (NMDA) and L-␣-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, has been put forth (7-9). Recent findings in mice with decreased NMDA receptor expression (10) confirmed and extended pr...

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Section: Psychostimulants Modulate Serotonergic Transmission In the Fsupporting

confidence: 61%

Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter

Gainetdinov

Mohn

Bohn

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

153

109

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“…The reason for this may lie in the proximal effect of the two drugs. Whilst the proximal effects of both MPH and d-amphetamine are mediated by DA and NA (Easton et al, 2007;Kuczenski & Segal, 1997), d-amphetamine also has significant effects on 5-HT (Holmes & Rutledge, 1976) at higher doses (Kuczenski & Segal, 1989), whereas the effect of MPH on 5-HT is less clear Kuczenski & Segal, 1997;Kuczenski et al, 1987). Amphetamine's stronger effects on 5-HT mediated transmission, which is uniformly depressant in the SC (Kawai & Yamamoto, 1969;Straschill & Perwein, 1971), may be sufficient to combat and overcome any facilitatory effects stemming from cortical activation.…”

Section: Overall Discussionmentioning

confidence: 99%

“…The proximal effects of MPH are mediated by increasing synaptic levels of the monoamines dopamine (DA) and noradrenaline (NA; Kuczenski & Segal, 1997;Easton et al, 2007) and possibly serotonin (5-HT; Kuczenski et al, 1987). Evidence suggests SC itself receives extensive noradrenergic (Lindvall & Bjorklund, 1974;Weller et al, 1987) and serotonergic (Parent et al, 1981;Weller et al, 1987) innervation, as well as a limited dopaminergic input (Weller et al, 1987;Campbell et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Effect of methylphenidate on visual responses in the superior colliculus in the anaesthetised rat: Role of cortical activation

et al. 2017

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The mechanism of action of psychostimulant drugs in the treatment of Attention Deficit Hyperactivity Disorder is still largely unknown, although recent evidence suggests one possibility is that the drugs affect the superior colliculus (SC). We have previously demonstrated that systemically administered d-amphetamine attenuates/abolishes visual responses to whole field light flashes in the superficial layers of the SC in anaesthetised rats, and the present study sought to extend this work to methylphenidate (MPH). Anaesthetised rats were administered MPH at a range of doses (or saline) and subjected to monocular whole field light flashes at two intensities, juxta-threshold and super-threshold. In contrast to d-amphetamine, systemic MPH produced an enhancement of visual activity at both intensities. Methylphenidate was also found to produce activation of the cortical EEG in anaesthetised rats. Furthermore, cortical activation induced by electrical stimulation of the pons was found enhance visual responses in superficial layers of the SC, and when MPH was paired with pontine-induced cortical activation, the response-enhancing effects of MPH were substantially attenuated. Taken together, the results suggest that the enhancement of visual responses in the superficial layers of the SC by MPH in the anaesthetised rat is an artefact of the drug's interaction with cortical arousal.

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“…For example Winstanley et al (2003) have found that effects of amphetamine, which also increases 5-HT transmission (Kuczenski et al, 1987), on intertemporal choice are attenuated by 5-HT depletion. One implication of this observation is that (some of) the calming, anti-impulsive effects of amphetamine administration in ADHD might be related to the drugs' enhancing effect on 5-HT transmission.…”

Section: Intertemporal Choicementioning

confidence: 99%

Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

Cools

Nakamura²,

Daw³

2010

Neuropsychopharmacol

409

369

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Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotoninFcomprising both affective and activational ones, as well as a number of other functions not overtly related to eitherFcan be seen as consequences of a single root mechanism.

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Effects of amphetamine, methylphenidate, and apomorphine on regional brain serotonin and 5-hydroxyindole acetic acid

Cited by 41 publications

References 39 publications

Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter

Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter

Effect of methylphenidate on visual responses in the superior colliculus in the anaesthetised rat: Role of cortical activation

Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions

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