Bi-directional effects of GABA(B) receptor agonists on the mesolimbic dopamine system.
paper
Cited
Public
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- Authors
- Cruz, Hans G; Ivanova, Tatiana; Lunn, Marie-Louise; Stoffel, Markus; Slesinger, Paul A; LΓΌscher, Christian
- Year
- 2004
- Journal
- Nature neuroscience
- PMID
- 14745451
- DOI
- 10.1038/nn1181
The rewarding effect of drugs of abuse is mediated by activation of the mesolimbic dopamine system, which is inhibited by putative anti-craving compounds. Interestingly, different GABA(B) receptor agonists can exert similarly opposing effects on the reward pathway, but the cellular mechanisms involved are unknown. Here we found that the coupling efficacy (EC(50)) of G-protein-gated inwardly rectifying potassium (GIRK, Kir3) channels to GABA(B) receptor was much lower in dopamine neurons than in GABA neurons of the ventral tegmental area (VTA), depending on the differential expression of GIRK subunits. Consequently, in rodent VTA slices, a low concentration of the canonical agonist baclofen caused increased activity, whereas higher doses eventually inhibited dopamine neurons. At behaviorally relevant dosages, baclofen activated GIRK channels in both cell types, but the drug of abuse gamma-hydroxy-butyric acid (GHB) activated GIRK channels only in GABAergic neurons. Thus GABA(B) receptor agonists exert parallel cellular and behavioral effects due to the cell-specific expression of GIRK subunits.
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| Evidence for oligomerization between GABAB receptors and GIRK channels containing the GIRK1 and GIRK3 subunits. | Ciruela F et al. | β | 2010 | β |
| Evolving therapeutic indications for N-type calcium channel blockers: from chronic pain to alcohol abuse. | Belardetti F | β | 2010 | β |
| GABAB receptor coupling to G-proteins and ion channels. | Padgett CL et al. | β | 2010 | β |
| GABAB receptor-dependent modulation of network activity in the rat prefrontal cortex in vitro. | Wang Y et al. | β | 2010 | β |
| GABA(B) receptor modulation of serotonin neurons in the dorsal raphΓ© nucleus and escalation of aggression in mice. | Takahashi A et al. | β | 2010 | β |
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| Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area. | Watson J et al. | β | 2010 | β |
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| Medication treatment of different types of alcoholism. | Johnson BA | β | 2010 | β |
| Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits. | Schwenk J et al. | β | 2010 | β |
| Plasticity of postsynaptic, but not presynaptic, GABAB receptors in SSADH deficient mice. | Vardya I et al. | β | 2010 | β |
| Residual social, memory and oxytocin-related changes in rats following repeated exposure to Ξ³-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination. | van Nieuwenhuijzen PS et al. | β | 2010 | β |
| Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities. | Bhave G et al. | β | 2010 | β |
| Substance P inhibits GABAB receptor signalling in the ventral tegmental area. | Xia YF et al. | β | 2010 | β |
| Behavioral effects of gamma-hydroxybutyrate, its precursor gamma-butyrolactone, and GABA(B) receptor agonists: time course and differential antagonism by the GABA(B) receptor antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348). | Koek W et al. | β | 2009 | β |
| Divergent regulation of GIRK1 and GIRK2 subunits of the neuronal G protein gated K+ channel by GalphaiGDP and Gbetagamma. | Rubinstein M et al. | β | 2009 | β |
| gamma-Hydroxybutyrate (GHB) induces GABA(B) receptor independent intracellular Ca2+ transients in astrocytes, but has no effect on GHB or GABA(B) receptors of medium spiny neurons in the nucleus accumbens. | MolnΓ‘r T et al. | β | 2009 | β |
| Ischaemia differentially regulates GABA(B) receptor subunits in organotypic hippocampal slice cultures. | Cimarosti H et al. | β | 2009 | β |
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| New sites of action for GIRK and SK channels. | LujΓ‘n R et al. | β | 2009 | β |
| Sedative and hypothermic effects of gamma-hydroxybutyrate (GHB) in rats alone and in combination with other drugs: assessment using biotelemetry. | van Nieuwenhuijzen PS et al. | β | 2009 | β |
| Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABA-activated GIRK channels in Purkinje cells. | FernΓ‘ndez-Alacid L et al. | β | 2009 | β |
| The distribution of gamma-hydroxybutyrate-induced Fos expression in rat brain: comparison with baclofen. | van Nieuwenhuijzen PS et al. | β | 2009 | β |
| The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. | Bradaia A et al. | β | 2009 | β |
| Absence and rescue of morphine withdrawal in GIRK/Kir3 knock-out mice. | Cruz HG et al. | β | 2008 | β |
| Addictive drugs modulate GIRK-channel signaling by regulating RGS proteins. | Lomazzi M et al. | β | 2008 | β |
| Baclofen and gamma-hydroxybutyrate withdrawal. | LeTourneau JL et al. | β | 2008 | β |
| Behavioral characterization of mice lacking GIRK/Kir3 channel subunits. | Pravetoni M et al. | β | 2008 | β |
| Cataleptic effects of gamma-hydroxybutyrate (GHB) and baclofen in mice: mediation by GABA(B) receptors, but differential enhancement by N-methyl-d-aspartate (NMDA) receptor antagonists. | Koek W et al. | β | 2008 | β |
| Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. | Aguado C et al. | β | 2008 | β |
| Chronic morphine exposure affects visual response latency of the lateral geniculate nucleus in cats. | Long Z et al. | β | 2008 | β |
| Differential involvement of GABA system in mediating behavioral and neurochemical effect of acupuncture in ethanol-withdrawn rats. | Lee BH et al. | β | 2008 | β |
| Ethanol effects on dopaminergic ventral tegmental area neurons during block of Ih: involvement of barium-sensitive potassium currents. | McDaid J et al. | β | 2008 | β |
| Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring. | Zupan B et al. | β | 2008 | β |
| Pre- and postsynaptic regulation of locus coeruleus neurons after chronic morphine treatment: a study of GIRK-knockout mice. | Torrecilla M et al. | β | 2008 | β |
| Quantitative trait locus and computational mapping identifies Kcnj9 (GIRK3) as a candidate gene affecting analgesia from multiple drug classes. | Smith SB et al. | β | 2008 | β |
| A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction. | Lunn ML et al. | β | 2007 | β |
| Chronic morphine exposure alters the dendritic morphology of pyramidal neurons in visual cortex of rats. | Li Y et al. | β | 2007 | β |
| Coregulation of natively expressed pertussis toxin-sensitive muscarinic receptors with G-protein-activated potassium channels. | Clancy SM et al. | β | 2007 | β |
| Effects of gamma hydroxybutyric acid on inhibition and excitation in rat neocortex. | Li Q et al. | β | 2007 | β |
| GABA(B) receptors: synaptic functions and mechanisms of diversity. | Ulrich D et al. | β | 2007 | β |
| RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. | LabouΓ¨be G et al. | β | 2007 | β |
| Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome. | Harashima C et al. | β | 2006 | β |
| Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression. | Bellone C et al. | β | 2006 | β |
| Distinct populations of spinal cord lamina II interneurons expressing G-protein-gated potassium channels. | Marker CL et al. | β | 2006 | β |
| GABA(B) receptors and synaptic modulation. | Kornau HC | β | 2006 | β |
| GABAB receptor stimulation accentuates the locomotor effects of morphine in mice bred for extreme sensitivity to the stimulant effects of ethanol. | Holstein SE et al. | β | 2006 | β |
| Gamma-hydroxybutyrate--a drug of abuse. | Drasbek KR et al. | β | 2006 | β |
| Hyperdopaminergia and altered locomotor activity in GABAB1-deficient mice. | Vacher CM et al. | β | 2006 | β |
| Metabolic GHB precursor succinate binds to gamma-hydroxybutyrate receptors: characterization of human basal ganglia areas nucleus accumbens and globus pallidus. | MolnΓ‘r T et al. | β | 2006 | β |
| Molecular diversity, trafficking and subcellular localization of GABAB receptors. | Bettler B et al. | β | 2006 | β |
| Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application. | Millan MJ | β | 2006 | β |
| The mechanistic classification of addictive drugs. | LΓΌscher C et al. | β | 2006 | β |
| Unravelling the brain targets of gamma-hydroxybutyric acid. | Crunelli V et al. | β | 2006 | β |
| beta-Arrestin2, interacting with phosphodiesterase 4, regulates synaptic release probability and presynaptic inhibition by opioids. | BradaΓ―a A et al. | β | 2005 | β |
| Chronic morphine exposure affects the visual response properties of V1 neurons in cat. | He L et al. | β | 2005 | β |
| Chronic morphine exposure induces degradation of receptive field properties of LGN cells in cats. | He LH et al. | β | 2005 | β |
| Decreased firing frequency of midbrain dopamine neurons in mice lacking mu opioid receptors. | Mathon DS et al. | β | 2005 | β |
| Degradation of response modulation of visual cortical cells in cats with chronic exposure to morphine. | He L et al. | β | 2005 | β |
| Dopamine responsiveness is regulated by targeted sorting of D2 receptors. | Bartlett SE et al. | β | 2005 | β |
| Endogenous RGS proteins enhance acute desensitization of GABA(B) receptor-activated GIRK currents in HEK-293T cells. | Mutneja M et al. | β | 2005 | β |
| Gamma-hydroxybutyric acid. | Snead OC et al. | β | 2005 | β |
| Gamma-hydroxybutyric acid (GHB) and the mesoaccumbens reward circuit: evidence for GABA(B) receptor-mediated effects. | Pistis M et al. | β | 2005 | β |
| mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors. | Bellone C et al. | β | 2005 | β |
| Molecular and cellular diversity of neuronal G-protein-gated potassium channels. | Koyrakh L et al. | β | 2005 | β |
| Spinal G-protein-gated potassium channels contribute in a dose-dependent manner to the analgesic effect of mu- and delta- but not kappa-opioids. | Marker CL et al. | β | 2005 | β |
| The role of GABA in the early neuronal development. | Jelitai M et al. | β | 2005 | β |
| Cocaine alters GABA(B)-mediated G-protein activation in the ventral tegmental area of female rats: modulation by estrogen. | Febo M et al. | β | 2004 | β |
| Correlating function and gene expression of individual basal ganglia neurons. | Liss B et al. | β | 2004 | β |
| Unravelling the unusual signalling properties of the GABA(B) receptor. | Couve A et al. | β | 2004 | β |
| Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. | Beckstead MJ et al. | β | 2004 | β |