Interactions between adenosine and dopamine receptor antagonists with different selectivity profiles: Effects on locomotor activity

Collins, Lyndsey E.; Galtieri, Daniel; Collins, Patricia; Jones, Shawnet K.; Port, Russell G.; Paul, Nicholas E.; Hockemeyer, Jörg; Müller, Christian; Salamone, John D.

doi:10.1016/j.bbr.2010.03.003

Cited by 47 publications

(35 citation statements)

References 77 publications

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“…MSX-3 also reversed the effects of the D 2 antagonists haloperidol and eticlopride in rats responding on the concurrent lever pressing/chow feeding procedure [ . Similar results were obtained with rats tested on a noveltyinduced locomotion procedure [124].…”

Section: Forebrain Circuits and Neurotransmitter Interactions Regulatinsupporting

confidence: 76%

“…Recently, it was demonstrated that either systemic or intra-accumbens injections of the adenosine A 2A receptor antagonist MSX-3 reversed the effects of intra-accumbens injections of the D 2 antagonist eticlopride on effort-related choice [84], demonstrating that nucleus accumbens is an important locus for this D 2 -A 2A interaction. Moreover, these results from studies of effort-related choice behavior are consistent with the large body of evidence demonstrating that A 2A antagonism can generally reverse the effects of D 2 antagonism across a wide range of behavioral contexts, including tasks that involve functions related to ventral and dorsal striatum [115,116,124,125]. The specificity of this interaction is possibly related to the pattern of cellular localization of adenosine A 1 and A 2A receptors in striatal areas, including the nucleus accumbens [103].…”

Section: Forebrain Circuits and Neurotransmitter Interactions Regulatinsupporting

confidence: 69%

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Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Salamone

Correa²,

Farrar³

et al. 2010

Future Neurol.

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Review Dopaminergic involvement in activational aspects of motivationSimilar to other psychological constructs such as emotion and cognition, motivation is not a simple or unitary phenomenon. Motivation is a complex and multifacted process that includes many diverse components. Some aspects of motivation are related to sensations of internal and external stimuli, while other aspects of motivation are related to motor function [1]. Motivated behavior takes place in phases that represent different degrees of physical or psychological distance from the primary motivational stimulus (i.e., appetitive vs consummatory; instrumental vs consummatory; see [2][3][4]). Moreover, motivation theory and research has emphasized for several years that there are 'directional' and 'activational' aspects of motivation [5][6][7]. Directional aspects refer to the observation that the behavior of animals is directed towards or away from particular motivational stimuli. In addition, it is evident that motivated behavior can be characterized by persistence, vigor and high levels of work output; these activational aspects of motivated behavior are highly adaptive because they enable organisms to overcome challenges or work-related response costs that separate them from significant stimuli such as food [4,[8][9][10][11][12][13]. While foraging in the wild, animals can invest considerable time and can cover large areas of space in order to gain access to food or other primary motivational stimuli. Laboratory experiments have shown that animals can climb barriers, run in mazes or press levers on schedules with high input ratio requirements, in order to gain access to motivational stimuli such as food. Under some conditions the presentation of motivational stimuli can generate heightened, even excessive, levels of motor activity. In humans, impairments in behavioral activation can manifest themselves as energy-related symptoms such as psychomotor slowing, anergia and fatigue, which are features of depression, and can also be observed in other psychiatric or n eurological disorders [11].In addition to studying these behavioral processes involved in activational aspects of motivation, neuroscientists have also focused upon the brain mechanisms that are potentially involved. Several brain areas have been investigated, but one of the neural systems most closely associated with behavioral activation is the dopamine (DA) innervation of the nucleus accumbens [8][9][10][11]14,15]. Although the mesolimbic DA system has consistently been linked to aspects of drug reinforcement, and is often referred to as some type of 'pleasure' or 'reward' center, recent Brain dopamine, particularly in the nucleus accumbens, has been implicated in activational aspects of motivation and effort-related processes. Accumbens dopamine depletions reduce the tendency of rats to work for food, and alter effort-related decision making, but leave aspects of food motivation such as appetite intact. Recent evidence indicates that the purine neuromodulator adenosine, largely thr...

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Section: Forebrain Circuits and Neurotransmitter Interactions Regulatinsupporting

confidence: 76%

Section: Forebrain Circuits and Neurotransmitter Interactions Regulatinsupporting

confidence: 69%

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Salamone

Correa²,

Farrar³

et al. 2010

Future Neurol.

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“…Unfortunately, the 0.3 mg/kg DPCPX dose completely suppressed the antidepressant-like effect of CHA. A more complete understanding of CHA and DPCPX pharmacological potency that was available after the jpet.aspetjournals.org present studies (Collins et al, 2010;Paul et al, 2011) were conducted suggests that the 0.3 mg/kg DPCPX dose results in maximal effects at blocking adenosine A 1 receptors. Furthermore, similar antidepressant-like effects of CHA alone were observed in this experiment both times the agonist was administered.…”

Section: Discussionmentioning

confidence: 85%

“…Third, although adenosine A 1 and adenosine A 2A receptors easily are the most abundant adenosine receptor subtypes found in the brain (Ribeiro et al, 2002), DPCPX (0.375-1.5 mg/kg i.p.) failed to attenuate the locomotor effects of the dopamine D 2 receptor antagonist eticlopride unlike an adenosine A 2A receptor antagonist (Collins et al, 2010). Unfortunately, the 0.3 mg/kg DPCPX dose completely suppressed the antidepressant-like effect of CHA.…”

Section: Discussionmentioning

confidence: 94%

Activation of Adenosine₁ Receptors Induces Antidepressant-Like, Anti-Impulsive Effects on Differential Reinforcement of Low-Rate 72-s Behavior in Rats

Marek

2012

J Pharmacol Exp Ther

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Stress and psychiatric illness have been associated with a dysregulation of glutamatergic neurotransmission. Recently, positive allosteric modulators (PAMs) of the metabotropic glutamate 2 (mGlu 2 ) receptor have been found to exert antidepressant-like activity in rats performing under a differential reinforcement of low rate (DRL) 72-s schedule. An autoreceptor role at glutamatergic synapses is the most salient physiological role played by the mGlu 2 receptor. Adenosine A 1 receptors play a heteroreceptor role at many of the same forebrain synapses where mGlu 2 autoreceptors are found. Agonists and/or PAMs of mGlu 2 receptors act similarly to adenosine A 1 receptor agonists with respect to a wide range of electrophysiological, biochemical, and behavioral responses mediated by limbic circuitry thought to play a role in the pathophysiology of neuropsychiatric disease and to mediate therapeutic drug effects. Therefore, the role of adenosine A 1 receptor activation on rat DRL 72-s behavior was explored to provide preclinical evidence consistent or inconsistent with potential antidepressant effects. The adenosine A 1 receptor agonist N 6 -cyclohexyladenosine (CHA) increased the reinforcement rate, decreased the response rate, and induced a rightward shift in inter-response time distributions in a dose-dependent fashion similar to most known antidepressant drugs. The adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked these antidepressant-like effects. These novel observations with CHA and DPCPX suggest that activation of adenosine A 1 receptors could contribute to antidepressant effects, in addition to previous preclinical reports of anxiolytic and antipsychotic effects. By implication, targeting a dysregulated glutamatergic system may be an important principle in discovering novel antidepressant agents that may also possess anti-impulsive activity.

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“…For instance, VMAT2 activity can be increased with the small molecule trkB agonist, 7,8-dihydroxyflavone, which was neuroprotective in a rodent model of PD (Jang et al, 2010). In addition to compounds that may increase DA availability and release, adenosine (A2A) receptor antagonists, which are thought to facilitate the activation of DA D2 receptors, are efficacious in reversing decreased effort-based sucrose consumption after DA depletion with tetrabenazine (a vesicular monoamine transporter inhibitor) and after peripheral administration of IL-1β in rats (Chen et al, 2001;Collins et al, 2010;Nunes et al, 2014;Xie et al, 2009;Yohn et al, 2015). The DA receptor agonist, pramipexole, has been shown to block endotoxin-induced degeneration of nigrostriatal DA cells (Iravani et al, 2008), and has also demonstrated the efficacy in unipolar and bipolar patients with treatment-resistant depression (Cassano et al, 2004;Cusin et al, 2013;Fawcett et al, 2016;Franco-Chaves et al, 2013).…”

Section: Strategies To Facilitate Da Packaging and Release Or Da Recementioning

confidence: 99%

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

Felger

Treadway

2016

Neuropsychopharmacol

318

237

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Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.

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Interactions between adenosine and dopamine receptor antagonists with different selectivity profiles: Effects on locomotor activity

Cited by 47 publications

References 77 publications

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Activation of Adenosine₁ Receptors Induces Antidepressant-Like, Anti-Impulsive Effects on Differential Reinforcement of Low-Rate 72-s Behavior in Rats

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

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Interactions between adenosine and dopamine receptor antagonists with different selectivity profiles: Effects on locomotor activity

Cited by 47 publications

References 77 publications

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Activation of Adenosine1 Receptors Induces Antidepressant-Like, Anti-Impulsive Effects on Differential Reinforcement of Low-Rate 72-s Behavior in Rats

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

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Product

Resources

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Activation of Adenosine₁ Receptors Induces Antidepressant-Like, Anti-Impulsive Effects on Differential Reinforcement of Low-Rate 72-s Behavior in Rats