Dopamine-Glutamate Interactions

Another feature of schizophrenia that cannot be explained well from a purely dopaminergic perspective is dysregulation of the dopamine system itself. Patients with schizophrenia show positive symptoms that are suggestive of underlying dopaminergic hyperactivity. Yet, despite decades of study, only few intrinsic deficits have been detected within the dopamine system that could account for this hyperactivity. For most patients, therefore, reasons for apparent dopaminergic hyperactivity remain unexplained. 

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Tseng K. Y. and O Donnell P. (2004). Dopamine-glutamate interactions controlling prefrontal cortical pyramidal cell excitability involve multiple signaling mechanisms. J. Neurosci. 24 ... 

Glutamate and Schizophrenia Phencyclidine, jV-methyl-D-aspartate Receptors, and Dopamine—Glutamate Interactions Daniel C. Javitt... 

Javitt DC. 2007. Glutamate and schizophrenia Phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol 78 69-108. 

Konradi C, Cepeda, Levine MS (2002) Dopamine-glutamate interactions. In Di Chiara G (Ed), Dopamine in the CNS II, pp. 117-133. Springer, Berlin. 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

Balfour DJ (2002) Neuroplasticity within the mesoaccumbens dopamine system and its role in tobacco Dependence, Curr Drug Targets CNS Neurol Disord 1 413-21 Balfour DJ (2004) The neurobiology of tobacco dependence a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6 899-912 Barik J, Wonnacott S (2006) Indirect modulation by alpha7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices interaction with glutamate and GABA systems and effect of nicotine withdrawal. Mol Pharmacol 69 618-628... 

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

Strong evidence indicates at least a familial pattern and perhaps a hereditary basis for some types of alcoholism ( 393). More recent data show that genotype accounts for approximately 33% of the overall variance in liability ( 394). In addition, specific neurocircuitry and neurochemical systems appear to be important in the etiology of alcoholism (395). Thus, positive reinforcement may be mediated by activation of g-aminobutyric acid (GABA) receptors, release of opioid peptides and dopamine, inhibition of glutamate receptors, and interactions with the 5-HT system. Furthermore, neurobehavioral effects of alcohol and their association with these various neurotransmitters serve as potential targets for novel drug therapies. 

The interaction of glutamate and its NMDA receptor with other brain neurotransmitters, including the aminergic dopamine and serotonin neuromodulators which are the main focus of this book, is very complex and only a few, simplified accounts of how NMDA receptor hypofunction... 

Alcamprosate, a derivative of the amino acid taurine, interacts with the NMDA receptor and perhaps can substitute for this effect of alcohol during abstinence (Fig. 13-30). Thus, when alcohol is withdrawn and the mesolimbic D2 receptors are whining for dopamine because of too much glutamate, perhaps alcamprosate substitution will reduce the neuronal hyperexcitability of alcohol withdrawal, resulting... 

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