Sensing dopamine

The phenylboronic acid conjugated coumarin probe 19 was constructed to sense dopamine and norepinephrine (Scheme 4.11). The boronic acid was incorporated as a recognition element into 19 to enhance both selectivity and affinity for dopamine and norepinephrine over other primary amines. 

Y.B. Zeng, Y. Zhou, L. Kong, T.S. Zhou and G.Y. Shi, A novel composite of SiO -coated graphene oxide and molecularly imprinted polymers for electrochemical sensing dopamine. Biosens. Bioelectron., 45 25-33, 2013. 

In 1954, experiments by Olds and Milner revealed that the brain has specialized centers for reward functions. In these studies electrical stimulation of certain brain sites was found to be highly rewarding in the sense that rats operantly respond for electrical stimulation of these brain sites, often to the exclusion of any other activity. A neurotransmitter system that is particularly sensitive to electrical self-stimulation is the mesolimbic dopamine projection that originates in the ventral tegmental area and projects to structures closely... 

Sibutramine and its two active metabolites (Mj and M2) exert their effect by inhibiting the reuptake of serotonin, norepinephrine, and dopamine.29 Appetite becomes suppressed because patients feel a sense of satiety. 

Several other organoboron polymers have been developed by various synthetic strategies and utilized to construct polymeric sensing systems for cations, dopamine, saccharides, and so on. Fabre and co-workers have reported the preparation of a conjugated trifluoroborate-substituted polythiophene system for sensing cations such as... 

Assuming that this explanation of Parkinson s disease is correct, a possible treatment for the condition is apparent Provide patients with an increased supply of dopamine. With additional levels of dopamine in the body, normal nerve function might be expected to be restored, and the symptoms of Parkinson s might be reduced. This form of therapy appears to make theoretical sense, and it has formed... 

Sexual receptivity. The effects of THC on sexual behavior in female rats and its influence on steroid hormone receptors and neurotransmitters in the facilitation of sexual receptivity was examined. Results revealed that the facilitatory effect of THC was inhibited by antagonists to both progesterone and dopamine D(l) receptors. To test further the idea that progesterone receptors (PR) and/or dopamine receptors (D[1]R) in the hypothalamus were required for THC-facilitated sexual behavior in rodents, antisense, and sense oligonucleotides to PR and D(1)R were administered intra-cerebroventricularly into the third cerebral ventricle of ovariectomized, estradiol benzoate-primed rats. Progesterone- and THC-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides to PR or to D(1)R. Antagonists to... 

Raj CR, Okajima T, Ohsaka T (2003) Gold nanoparticle arrays for the voltammetric sensing of dopamine. J Electroanal Chem 543 127-133... 

But the fact that we experience anxiety—often of panic proportions in our REM sleep dreams when the locus coeruleus is shut down completely—means two things that arousal—at least in the waking sense of the term—and anxiety are completely dissociable and that the brain-mind is capable of generating anxiety without the help of the locus coeruleus In fact, REM sleep dream anxiety cannot depend upon norepinephrine, or serotonin, or histamine either, which leaves dopamine and acetylcholine as the only two neuromodulatory candidates for... 

The unpleasant aspects of LSD psychosis, and especially the sense of ego dissolution that Hofmann so vividly described, are reasonably ascribed to LSD-enhancement of the dopamine system. Based upon the strong correlation between the dopamine-blocking properties of drugs and their antipsychotic potency, scientists have long held that schizophrenia may be mediated by abnormal dopamine neurotransmission. 

The reason that the illicit use of these drugs is so difficult to curb is not only because they elevate vigilance, but also because they greatly enhance mental energy, elevate mood, increase physical strength, and maximize sexual potency. This sounds like a dream, in the metaphorical sense, and indeed, some actual dreams have these desirable qualities, but the stimulants do not produce otherwise dreamlike mentation even when they trigger psychoses. The similarities between dopamine and cocaine can be appreciated in figure 15.2. 

Cocaine (Fig. 13—3) has two major properties it is both a local anesthetic and an inhibitor of monoamine transporters, especially dopamine (Fig. 13—4). Cocaine s local anesthetic properties are still used in medicine, especially by ear, nose, and throat specialists (otolaryngologists). Freud himself exploited this property of cocaine to help dull the pain of his tongue cancer. He may have also exploited the second property of the drug, which is to produce euphoria, reduce fatigue, and create a sense of mental acuity due to inhibition of dopamine reuptake at the dopamine transporter. Cocaine also has similar but less important actions at the norepinephrine and the serotonin transporters (Fig. 13—3). Cocaine may do more than merely block the transporter—it may actually release dopamine (or norepinephrine or serotonin) by reversing neurotransmitter out of the presynaptic neuron via the monoamine transporters (Fig. 13—4). 

FIGURE 13—4. Pharmacology of cocaine. Cocaine is a powerful inhibitor of the dopamine transporter. Blocking this transporter acutely causes dopamine to accumulate, and this produces euphoria, reduces fatigue, and creates a sense of mental acuity. Cocaine has similar but less important actions at the norepinephrine and serotonin transporters. 

FIGURE 13-18. Pharmacology of nicotine (part 1). Nicotine acts directly on nicotinic cholinergic receptors, which are themselves located in part on mesolimbic dopamine neurons. When nicotine stimulates these receptors (A and B), it causes release of dopamine from the mesolimbic neurons and thereby conveys a sense of reward and pleasure. 

By now you have a sense of the interwoven roles of dopamine, norepinephrine, and acetylcholine in the control of movement, reward, mood, arousal, and learning and attention. By considering how various drugs manipulate these neurotransmitter systems within the brain, scientists have discovered some consistent patterns that allow us to make predictions about what to expect when specific types of drugs are taken. The same holds true for the neurotransmitter system mentioned several times in this chapter serotonin. What are the consequences of its manipulation in the brain Read on. 

One of the more serious problems occurring from the use of antipsychotics is the production of abnormal movement patterns.36,44 Many of these aberrant movements are similar to those seen in patients with lesions of the extrapyramidal system and are often referred to as extrapyramidal side effects. The basic reason that these motor problems occur is because dopamine is an important neurotransmitter in motor pathways, especially in the integration of motor function that takes place in the basal ganglia. Because antipsychotic drugs block CNS dopamine receptors, it makes sense that... 

This effect is not surprising Amphetamines are potent psychomotor stimulants. Whether sniffed, swallowed, snorted, or injected, they induce feelings of power, strength, exhilaration, self-assertion, focus, and enhanced motivation. Amphetamine intake causes a release of the excitatory neurotransmitters dopamine and noradrenaline (norepinephrine) in the central nervous system (CNS). The release of dopamine typically induces a sense of aroused euphoria that may last several hours unlike cocaine, amphetamine is not readily broken down by the body. After taking amphetamines, feelings are intensified, the need to sleep or eat is diminished, and the user may feel as though he or she can take on the world. ... 

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