Dopamine neurotransmission

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

Paulson P. E., Robinson T. E. (1994). Relationship between circadian changes in spontaneous motor activity and dorsal versus ventral striatal dopamine neurotransmission assessed with on-line microdialysis. Behav. Neurosci 108(3),... 

Itiee, J. M., et ah. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet, 2003, 12(18), 2277-91. 

Devine DP, Leone P, Wise RA. (1993). Mesolimbic dopamine neurotransmission is increased by administration of mu-opioid receptor antagonists. EurJ Pharmacol. 243(1) 55-64. 

Mechanism of Action A phenothiazine that blocks dopamine neurotransmission at postsynaptic dopamine receptor sites. Possesses strong anticholinergic, sedative, and antiemetic effects moderate extrapyramidal effects and slight antihistamine action. Therapeutic Effect Relieves nausea and vomiting improves psychotic conditions controls intractable hiccups and porphyria. 

Mechanism of Action A general anesthetic and antiemetic agent that antagonizes dopamine neurotransmission at synapses by blocking postsynaptic dopamine receptor sites partially blocks adrenergic receptor binding sites. Therapeutic Effect Produces tranquilization, antiemetic effect. 

Jeffrey W. Dailey and his colleagues use animal models and imaging to show that the physiological state of dopamine neurotransmission may be an important factor in substance abuse problems. 

Dailey, Jeffrey W., Tim D. Fryer, Laurent Brichard, Emma S. J. Robinson, David E. H. Theobald, Kristjan La e, et al. Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement. Science 315 (March 2,2007) 1,267-1,270. The researchers report on evidence that indicates the state of dopamine neurotransmission may be an important factor leading to substance abuse problems. 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

Paulson, Pamela E., and Terry E. Robinson. 1995. "Amphetamine-Induced Time-Dependent Sensitization of Dopamine Neurotransmission in the Dorsal and Ventral Striatum A Microdialysis Study in Behaving Rats." Synapse 19 56-65. 

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. 

Zimmer L., Delion-Vancassel S., Durand G., Guilloteau D., Bodard S., Besnard J. C., and Chalon S. (2000). Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J. Lipid Res. 41 32 10. 

Bamford NS, Zhang H, Schmitz Y, Wu NP, Cepeda C, Levine MS, Schmauss C, Zakharenko SS, Zablow L, Sulzer D (2004) Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals. Neuron 42 653-63... 

Drug-induced disruption of dopamine neurotransmission is known to produce a variety of neurological side effects (see chapters 3 and 5). The neuroleptics suppress dopamine neurotransmission, causing a reactive hyperactivity of the system that produces a high rate of irreversible dyskinesias, cognitive dysfunction, and dementia. 

Ungerstedt, V., Ljungberg, T. (1977). Behavioral patterns related to dopamine neurotransmission Effect of acute and chronic antipsychotic drugs. Advances in Biochemical Psychopharmacology, 16, 193-199. 

The C and R subunits are encoded by three (a, (3, y) and four (lot, 1(3, Hot, 11(3) genes, respectively (Tasken et al., 1997). In striatal areas, Ca, C(3 and RII(3 are the predominantly expressed isoforms (Brandon et al., 1997). The mice deficient in functional RII(3 subunit show a decreased PKA activity in the striatum and exhibit behavioral modifications that suggest an alteration in their dopamine neurotransmission (Brandon et al., 1998). In neurons, the presence of RII targets the PKA towards the postsynaptic densities whereas PKA containing RI subunits are essentially localized in the cytoplasm (Corbin et al., 1977 Deviller et al., 1984). The association of RII subunits with these subcellular compartments is due to their interaction with A kinase attachment proteins (AKAP) (Carr et al., 1992 ... 

The use of dopamine receptor knockout mice in understanding brain dopamine neurotransmission and sprouting in the nigrostriatal pathway... 

Consistent with the documented expression of the D3R in nigrostriatal projection neurons, D3R(—/—) mice were shown to have abnormal dopamine neurotransmission. The locomotor hyperactivity was associated with elevated extracellular dopamine levels as measured by in vivo microdialysis (Joseph et al., 2002). Evoked dopamine release studied in striatal brain slices showed that the effect of the D2R/D3R agonist quinpirole in inhibiting dopamine release was mildly reduced in D3R(—/—) mice confirming that this receptor at least participated in D2-like dopamine autoreceptor functionality. 

The behavioral and functional consequences of dopamine receptor activation have been extensively examined and reported and some of these studies have already been discussed above. However the regulation of the size of the terminal arbor of dopamine neurons is mediated by dopamine receptors. This phenomenon has recently been reported (Finkelstein, 2002) and has significant ramifications for the behavioral effects mediated by dopamine and also in the interpretation of studies examining dopamine neurotransmission. The following section is a discussion and review of the role of dopamine receptors on the regulation of sprouting of dopaminergic neurons and axons. 

Robinson TE, Jurson PA, Bennett JA, Bentgen KM (1988) Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by prior experience with (+)-amphetamine a microdialysis study in freely moving rats. Brain Res 462 211-222. 

One of the major problems in thinking about dopamine neurotransmission is the number of features which do not fit into the textbook model of classical synaptic transmission, based on the neuromuscular junction. These include an extremely wide divergence of release sites of a single axon, extrasynaptic location of receptors, termination of neurotransmitter action by diffusion and uptake from extrasynaptic sites, and significant overflow of neurotransmitter from the synaptic cleft into the extracellular space. 

In this chapter, we undertake a review of the quantitative aspects of dopamine neurotransmission of relevance to the spatial and temporal specificity of the dopamine signal. The kinetics of dopamine release and clearance are considered in order to estimate the temporal and spatial concentration distribution of dopamine. The location of receptors and their sensitivity to dopamine are taken into account. We then consider the regulation of ion channels by the G proteins activated by dopamine, and how this might explain the effects of dopamine on the whole cell. Finally, we consider the regulation by dopamine of corticostriatal inputs to the spiny cells. 

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