Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain

Chernoloz, Olga; Mansari, Mostafa El; Blier, Pierre

doi:10.1503/jpn.110038

Cited by 33 publications

(20 citation statements)

References 68 publications

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“…However, Chernoloz and colleagues have recently shown that chronic pramipexole treatment also produces desensitization of presynaptic D2/3 and 5-HT1A auto-receptors and decreased sensitivity of presynaptic NE α2 receptors, leading to enhanced DA, 5-HT and possibly, NE release (Chernoloz et al, 2009, 2012). Desensitization of presynaptic D2/3 and NE α2 autoreceptors would likely lead to enhanced DA and NE signaling in response to cocaine or other reinforcing stimuli as well.…”

Section: Discussionmentioning

confidence: 99%

Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans

Newton

Haile

Mahoney

et al. 2015

Psychiatry Research

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Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine’s reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0 mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40 mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine.

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Section: Discussionmentioning

confidence: 99%

Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans

Newton

Haile

Mahoney

et al. 2015

Psychiatry Research

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“…In the current sample of early-stage PD patients, who had only recently begun DA replacement therapy, however, mean ventral striatal FDOPA K I values were very similar to those of healthy controls (Whone et al, 2004) and were unrelated to severity of PD. In animal models, there is some evidence that repeated treatments with DA agonist drugs can enhance basal DA synthesis in the VS (Rowlett et al, 1997) and frontal cortex (Chernoloz et al, 2012). However, other studies show persistent inhibition of DA synthesis following repeated treatment with DA agonists (Imperato et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Ventral Striatal Dopamine Synthesis Capacity Predicts Financial Extravagance in Parkinson’s Disease

Lawrence¹,

Brooks²,

Whone³

2013

Front. Psychol.

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Impulse control disorders (ICDs), including disordered gambling, can occur in a significant number of patients with Parkinson’s disease (PD) receiving dopaminergic therapy. The neurobiology underlying susceptibility to such problems is unclear, but risk likely results from an interaction between dopaminergic medication and a pre-existing trait vulnerability. Impulse control and addictive disorders form part of a broader psychopathological spectrum of disorders, which share a common underlying genetic vulnerability, referred to as externalizing. The broad externalizing risk factor is a continuously varying trait reflecting vulnerability to various impulse control problems, manifested at the overt level by disinhibitory symptoms and at the personality level by antecedent traits such as impulsivity and novelty/sensation seeking. Trait “disinhibition” is thus a core endophenotype of ICDs, and a key target for neurobiological investigation. The ventral striatal dopamine system has been hypothesized to underlie individual variation in behavioral disinhibition. Here, we examined whether individual differences in ventral striatal dopamine synthesis capacity predicted individual variation in disinhibitory temperament traits in individuals with PD. Eighteen early-stage male PD patients underwent 6-[18F]Fluoro-l-DOPA (FDOPA) positron emission tomography scanning to measure striatal dopamine synthesis capacity, and completed a measure of disinhibited personality. Consistent with our predictions, we found that levels of ventral, but not dorsal, striatal dopamine synthesis capacity predicted disinhibited personality, particularly a propensity for financial extravagance. Our results are consistent with recent preclinical models of vulnerability to behavioral disinhibition and addiction proneness, and provide novel insights into the neurobiology of potential vulnerability to impulse control problems in PD and other disorders.

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“…with MDD, leads to delayed enhancement of the firing of 5-HT and a desensitization of the 5-HT 1A autoreceptor and a net increase in 5-HT transmission [27,28]. The atypical antipsychotic quetiapine, which is an antidepressant in monotherapy at subtherapeutic doses for schizophrenia, increases net 5-HT and NE transmission in the rat hippocampus [29].…”

Section: Commonality Of Antidepressant Strategies On the 5-ht Systemmentioning

confidence: 99%

“…In such structures, or their equivalent in the rat brain, 5-HT, NE and DA generally exert an inhibitory action on neuronal firing as shown by their direct microiontophoretic application in vivo [13,16,28]. Consequently, the antidepressant response may be triggered by medications potentiating inhibitory transmission in limbic structures through one or more of these monoaminergic systems.…”

Section: The Forebrain Structures Involved In the Antidepressant Respmentioning

confidence: 99%

Serotonin and beyond: therapeutics for major depression

Blier

Mansari

2013

Phil. Trans. R. Soc. B

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215

136

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The serotonin (5-HT, 5-hydroxytryptamine) system has been implicated in the pathogenesis of major depressive disorder (MDD). The case for its contribution to the therapeutic efficacy of a wide variety of antidepressant treatments is, however, much stronger. All antidepressant strategies have been shown to enhance 5-HT transmission in the brain of laboratory animals. Catecholamines, norepinephrine (NE) and dopamine (DA) can also play a pivotal role in the mechanism of action of certain antidepressant strategies. The enhancement of 5-HT transmission by selective serotonin reuptake inhibitors, which leads to a dampening of the activity of NE and DA neurons, may account in part for the low remission rate achieved with these medications and/or the residuals symptoms after remission is achieved. The functional connectivity between the 5-HT, NE and DA systems can be used to understand the mechanism of action of a wide variety of augmentation strategies in treatment-resistant MDD. Proof-of-concept studies have shown that antidepressant medications with complementary mechanisms of action on monoaminergic systems can double the remission rate achieved in a trial of standard duration. Novel approaches are also being used to treat MDD, which also appear to involve the monoaminergic system(s) to a varying extent.

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Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain

Cited by 33 publications

References 68 publications

Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans

Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans

Ventral Striatal Dopamine Synthesis Capacity Predicts Financial Extravagance in Parkinson’s Disease

Serotonin and beyond: therapeutics for major depression

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