Dopamine-Adenosine Interactions | Bachtell Laboratory | University of Colorado Boulder
Caffeine and Adenosine - Caffeine and dopamine are related to the brain's pleasure centers. Learn about the relationship between caffeine and dopamine on. The interactions between adenosine and dopamine receptors in the striatum the link between A2A and dopamine D2 receptors was further strengthened. Dopamine appeared very early in the course of evolution and is involved in many functions that are essential for survival of the organism, such as motricity.
Caffeine also causes the brain's blood vessels to constrict, because it blocks adenosine's ability to open them up. This effect is why some headache medicines like Anacin contain caffeine -- constricting blood vessels in the brain can help stop a vascular headache. Caffeine's effect on the brain causes increased neuron firing. The pituitary gland senses this activity and thinks some sort of emergency must be occurring, so it releases hormones that tell the adrenal glands to produce adrenaline epinephrine.
Adrenaline is the " fight or flight " hormone, and it has a number of effects on your body: The airway opens up this is why people suffering from severe asthma attacks are sometimes injected with epinephrine.
Your heart beats faster. Blood vessels on the surface constrict to slow blood flow from cuts and increase blood flow to muscles. Blood flow to the stomach slows.
The liver releases sugar into the bloodstream for extra energy.This is your brain on caffeine
Muscles tighten up, ready for action. This explains why, after consuming a big cup of coffee, your hands get cold, your muscles grow tense, you feel excited and your heart beats faster. Adenosine isn't the only neurotransmitter affected by caffeine. Studies using slow-motion or freeze-frame video analyses, as well as electromyographic methods, have shown that these movements occur largely in the 3- to 7-Hz range that is also characteristic of parkinsonian resting tremor [ 44 - 47 ].
TJMs can be induced by striatal DA depletions [ 3745 ] and by centrally acting cholinomimetic drugs [ 24448 - 51 ]. They are also induced by typical antipsychotics, such as haloperidol [ 2252 ], pimozide [ 4648 ] and reserpine [ 47 ], but not by atypical antipsychotics [ 5253 ].
Evidence for adenosine/dopamine receptor interactions: indications for heteromerization.
Although chronic administration of antipsychotic drugs can result in oral movements that may be related to other movement disorders, such as tardive dyskinesia, considerable evidence indicates that the chewing-like jaw movements induced by acute or subchronic administration of typical antipsychotic drugs share many characteristics with parkinsonian symptoms [ 244464751 ]. TJMs have been used as a rodent model of parkinsonian tremor for assessing antiparkinsonian drugs with various pharmacological profiles [ 4474851 ].
The adenosine A2A antagonist KF In a recent series of experiments, the potential antiparkinsonian effects of the selective adenosine A2A antagonist MSX-3 were assessed by using acute or subchronic administration of antipsychotic drugs to induce TJMs [ 55 ]. In the first group of studies, pimozide Orap was used to induce motor impairments.
Moreover, pimozide has been reported to be more likely to produce parkinsonian tremor compared with other typical antipsychotics [ 56 ]. In recent papers, it was demonstrated that pimozide could induce TJMs with acute or subchronic administration i.
Based on these previous experiments, the first group of studies assessed the ability of adenosine A2A antagonism to suppress tremulous movements and increase motor activity in pimozide-treated rats [ 55 ]. In these studies, rats were injected with 1. After receiving these drug treatments, the rats were assessed with a battery of motor tests that included observations of TJMs, catalepsy and locomotor activity. Administration of both KW and MSX-3 suppressed pimozide-induced TJMs, and also reduced catalepsy and increased locomotion in the pimozide-treated rats [ 55 ].
An additional experiment investigated the effects of intracranial injections of MSX-3 into the VLS, in order to determine whether local injections of an adenosine A2A antagonist could reverse the TJMs induced by pimozide [ 55 ]. The VLS was chosen because this brain area, which is thought to be the homologue of the ventral putamen in primates, has been strongly implicated in the control of TJM activity [ 343744495457 ].
This experiment demonstrated that injections of MSX-3 into the VLS were able to suppress pimozide-induced TJMs [ 55 ], which was consistent with an earlier study showing that injections of an adenosine A2A antagonist into the VLS could reduce the TJMs induced by the cholinomimetic drug tacrine [ 54 ]. Discussion Taken together, the results of these experiments indicate that adenosine A2A antagonism can reverse locomotor suppression and tremulous movements induced by typical antipsychotics [ 223055 ].
These effects are consistent with the hypothesis that blockade of adenosine A2A receptors can produce antiparkinsonian effects in animal models. Adenosine A2A antagonists may be useful clinically for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms [ 223055 ].
Moreover, these experiments indicate that different striatal subregions are involved in distinct aspects of motor function. This principle has been demonstrated clearly in the substantial literature showing that DA depletions or antagonism can have regionally specific effects [ 283758 ], and it has important implications for understanding the anatomical mechanisms underlying the motor effects of antiparkinsonian drugs, including adenosine A2A antagonists.
Although antiparkinsonian drugs are typically given systemically, with the intention of producing an improvement in several different motor symptoms, it is nevertheless reasonable to suggest that different therapeutic effects i. In addition to studying these specific aspects of motor function, future research should also investigate the potential role of adenosine A2A receptors in motivational functions that are impaired in parkinsonism, such as psychomotor activation and effort-related processes [ 59 ].
Acknowledgements This research was supported by a grant to J. Footnotes Conflict of interest: The authors have declared no conflicts of interest. References  DeLong MR. Primate model of movement disorders of basal ganglia origin.
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