Dopamine control

Because it was known by 1960 that the pontine brain stem was crucial to REM sleep generation, it was natural to assume that the newly discovered modulatory elements played an important role in its generation. It was even reasonable, on an a priori basis, that each of the elements had responsibility for one state, viz, dopamine controls waking, serotonin controls slow wave sleep, and norepinephrine controls REM. Early lesion and parenteral pharmacological studies—some even armed with measures of amine concentrations in the brain—gave initial support to this concept. For example, Michel Jouvet produced insomnia in cats by blocking the enzyme that is essential to convert tryptophane into serotonin. He interpreted this result to mean that serotonin was a sleep mediator. 

Carbidopa is often coadministered with L-dopa to reduce the amount of l-dopa converted to dopamine in the periphery. Carbidopa thereby increases l-dopa s effectiveness and reduces its associated side effects, including nausea, vomiting, and loss of appetite. This compound blocks the action of the enzyme dopa-decarboxylase, which converts L-dopa into dopamine. Controlled-release Sinemet is a combination of L-dopa and carbidopa, with an extended half-life of immediate-acting combination products, producing an increased duration of effect. A combination of immediate-acting and controlled-release L-dopa and carbidopa is often used. In a number of patients, administration of the controlled-release pill only results in an insufficient conversion of central dopamine (93). The most common side effects associated with the administration of l-... 

Figure 3. Effect of increasing concentrations of dopamine on basal (A) and (—fisoproterenol-induced (B) cyclic AMP levels in rat pars intermedia cells in culture. Cells were incubated for 30 min in DMEM containing 5 mM HEPES, 100 pM ascorbic acid, and the indicated concentrations of dopamine alone (A). In B, 30 nM (—(isoproterenol was present during the last 4 min of incubation. Data are expressed as percent of control (in the absence of dopamine). Control cyclic AMP levels were 0.96 0.10 and 5.29 0.13 pmol/2 X 10s cells in the absence (A) or presence (B) of 30 M (—(isoproterenol, respectively (41).

Balter, Michael (1996). New Clues to Brain Dopamine Control, Cocaine Addiction. Science 271 909. 

For the detection of dopamine, controlled-potential (potentiostatic) techniques, which are concerned with the study of charge transfer processes at the electrode-solution interface, are favored due to a number of advantages. These include high sensitivity, selectivity towards electroactive species, wide linear range, portability and low cost of instrumentation, speciation capability and a wide range of electrodes which allow assays of unusual environments [29]. 

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

The nigrostriatal system is predominantly involved in motor control, which is particularly evident in Parkinson s disease (PD), where a progressive loss of these neurons results in loss of motor function. In the early stages of the disorder, the motor impairment can be reversed by the administration of the dopamine precursor l-DOPA (L-3,4-dihydroxyphenylalanine), which bypasses the need for TH in dopamine... 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

The transporters for 5HT, noradrenaline and dopamine, biogenic monoamines, are genetically related, exist as single isoforms and are expressed on the surface of nerve cells, which use monoamines as (or convert them into) their cognate neurotransmitter. The single-isoform monoamine transporters fulfil all three fundamental functions (reuptake, limiting synaptic transmission, and control of the extracellular neurotransmitter concentration). Inactivation of DAT, NET, or SERT results in an increased extracellular lifetime and level of monoamine neurotransmitter, but decreased intracellular storage and evoked release (Fig. 3). 

ADHD because cognitive functions known to be affected in this disorder, namely working memory and inhibitory control, are sensitive to manipulations of D1 receptor-mediated dopamine transmission [1]. Thus, the tonic component might be more critical for the behavioral functions of the FC. 

Another theory for the action of stimulant diugs in ADHD involves effects on nonstiiatal monoamine systems. Frontal cortical dopamine, norepinephrine, and serotonin are clearly important in cognitive functioning and impulse control. These neurotransmitters directly modulate reward-related behaviors associated with the striatal dopamine system. Moreover, the amygdala may be pharmacologically influenced leading to enhanced... 

Dysfunction of cortical-subcortical dopamine systems is associated with an impaired inhibitory control after chronic drug administration. 

An important clinical clue connected with the difference between tonic and phasic dopamine release is the so-called rate dependence of psychostimulant action. That means, it depends on the actual dopaminergic state (tonic and phasic) how an individual will react to psychostimulants. Figure 3 illustrates this rule by some examples [2]. The arrows represent the response of each component to methylphenidate for each of the classes of subjects tested, with the horizontal dashed line representing the baseline tonic andphasic levels present in control individuals. Summarizing, methylphenidate tends to normalize dopamine transmission regardless what the baseline rate is. 

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