Understanding Addiction: Author Theresa Brown Responds.

Understanding addiction: author Theresa Brown responds.

Filed under: Addiction Rehab

Am J Nurs. 2013 Jan; 113(1): 12
Brown T

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Rising taurine and ethanol concentrations in nucleus accumbens interact to produce the dopamine-activating effects of alcohol.

Filed under: Addiction Rehab

Adv Exp Med Biol. 2013; 775: 215-23
Ericson M, Chau P, Adermark L, Söderpalm B

Alcohol misuse and addiction is a worldwide problem causing enormous individual suffering as well as financial costs for the society. To develop pharmacological means to reduce suffering, we need to understand the mechanisms underlying the effects of ethanol in the brain. Ethanol is known to increase extracellular levels of both dopamine and taurine in the nucleus accumbens (nAc), a part of the brain reward system, but the two events have not been connected. In previous studies we have demonstrated that glycine receptors in the nAc are involved in modulating both basal- and ethanol-induced dopamine output in the same brain region. By means of in vivo microdialysis in freely moving rats we here demonstrate that the endogenous glycine receptor ligand taurine mimics ethanol in activating the brain reward system. Furthermore, administration of systemic ethanol diluted in an isotonic (0.9% NaCl) or hypertonic (3.6% NaCl) saline solution was investigated with respect to extracellular levels of taurine and dopamine in the nAc. We found that ethanol given in a hypertonic solution, contrary to an isotonic solution, failed to increase concentrations of both taurine and dopamine in the nAc. However, a modest, non-dopamine elevating concentration of taurine in the nAc disclosed a dopamine elevating effect of systemic ethanol also when given in a hypertonic solution. We conclude that the elevations of taurine and dopamine in the nAc are closely related and that in order for ethanol to induce dopamine release, a simultaneous increase of extracellular taurine levels in the nAc is required. These data also -provide support for the notion that the nAc is the primary target for ethanol in its dopamine-activating effect after systemic administration and that taurine is a prominent participant in activating the brain reward system.
HubMed – addiction

Neuropsychopharmacological actions of taurine.

Filed under: Addiction Rehab

Adv Exp Med Biol. 2013; 775: 3-18
Banerjee SP, Ragnauth A, Chan CY, Agovic MS, Sostris V, Jashanmal I, Vidal L, Friedman E

Taurine, an endogenous amino sulfonic acid, exhibits numerous neuropsychopharmacological activities. Previous studies in our laboratory have shown that it is an effective anti-cataleptic and neuro-protective agent. Current investigations show that acute or chronic administration of psychotropic drug cocaine may increase extracellular release of endogenous taurine which may protect against deleterious effects of the substances of abuse. Taurine administration was found to prevent cocaine-induced addiction by suppressing spontaneous locomotor activity and conditioned place preference. Taurine markedly delayed tail-flick response in rats which was significantly different from that in the group of animal receiving the same volume of saline, thereby indicating that taurine is a potentially valuable analgesic agent. Both taurine and endomorphin-1 were found to suppress the delayed broad negative evoked field potentials in anterior insular cortex (upper layer 5) by partially inhibiting NMDA receptor system. Thus, taurine is a unique psychopharmacological compound with potential for a variety of therapeutic uses including as a neuro-protective, anti-cataleptic, anti-addicting, and analgesic agent.
HubMed – addiction

Inositol 1,4,5-triphosphate drives glutamatergic and cholinergic inhibition selectively in spiny projection neurons in the striatum.

Filed under: Addiction Rehab

J Neurosci. 2013 Feb 6; 33(6): 2697-708
Clements MA, Swapna I, Morikawa H

The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this study, using mouse striatal slices, we show that glutamatergic and cholinergic inputs exert direct inhibitory regulation of SPN activity via activation of metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. While pressure ejection of the group I mGluR (mGluR1/5) agonist DHPG [(S)-3,5-dihydroxyphenylglycine] equally engages both mGluR1 and mGluR5 subtypes, the mGluR-dependent component of IPSCs elicited by intrastriatal electrical stimulation is almost exclusively mediated by the mGluR1 subtype. Ca(2+) release from intracellular stores specifically through inositol 1,4,5-triphospahte receptors (IP(3)Rs) and not ryanodine receptors (RyRs) mediates this form of inhibition by gating two types of Ca(2+)-activated K(+) channels (i.e., small-conductance SK channels and large-conductance BK channels). Conversely, spike-evoked Ca(2+) influx triggers Ca(2+) release solely through RyRs to generate SK-dependent slow afterhyperpolarizations, demonstrating functional segregation of IP(3)Rs and RyRs. Finally, IP(3)-induced Ca(2+) release is uniquely observed in SPNs and not in different types of interneurons in the striatum. These results demonstrate that IP(3)-mediated activation of SK and BK channels provides a robust mechanism for glutamatergic and cholinergic inputs to selectively suppress striatal output neuron activity.
HubMed – addiction

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