Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

Gantz, Stephanie C.; Levitt, Erica S.; Llamosas, Nerea; Neve, Kim A.; Williams, John T.

doi:10.1016/j.celrep.2015.07.005

Cited by 33 publications

(28 citation statements)

References 46 publications

(71 reference statements)

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“…The durations of D2S, D2L, and wild type D2 receptor-mediated spontaneous IPSCs were identical ( Figure 1F , [from Gantz et al, 2013 , WT: 515 ± 17 ms, n = 76 sIPSCs]). Amplitude and frequency of spontaneous IPSCs are affected by the level of D2 receptor expression and dopamine synthesis ( Gantz et al, 2013 , 2015 ). Since these parameters may be influenced by variegated viral infection, the amplitude and frequency of D2S- and D2L-sIPSCs were not compared.…”

Section: Resultsmentioning

confidence: 99%

Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

Gantz

Robinson

Buck

et al. 2015

eLife

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D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors.DOI: http://dx.doi.org/10.7554/eLife.09358.001

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Section: Resultsmentioning

confidence: 99%

Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

Gantz

Robinson

Buck

et al. 2015

eLife

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“…Given that some VTA neurons have very little SK-mediated current (Wolfart et al, 2001), the activation of mGluRs would disinhibit cells through the calcium-mediated inhibition of GIRK-dependent synaptic currents. Furthermore, many neurons have functional GIRK currents and IP 3 receptors, such as hippocampal pyramidal cells (Nakamura et al, 2000; Degro et al, 2015) and 5-HT neurons of the dorsal raphe (Gantz et al, 2015a; Pan et al, 1994). Thus the interaction between calcium release from stores and GIRK channel currents described here may not be a dopamine neuron-specific effect.…”

Section: Discussionmentioning

confidence: 99%

Calcium Release from Stores Inhibits GIRK

Kramer

Williams

2016

Cell Reports

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Summary Synaptic transmission is mediated by ionotropic and metabotropic receptors that together regulate the rate and pattern of action potential firing. Metabotropic receptors can activate ion channels and modulate other receptors and channels. The present paper examines the interaction between group 1 mGluR-mediated calcium release from stores, and GABAB/D2 mediated GIRK currents in rat dopamine neurons of the Substantia Nigra. Transient activation of mGluRs decreased the GIRK current evoked by GABAB and D2 receptors, though less efficaciously for D2. The mGluR-induced inhibition of GIRK current peaked in 1 second and recovered to baseline after 5 seconds. The inhibition was dependent on release of calcium from stores, was larger for transient than for tonic currents, and was unaffected by inhibitors of PLC, PKC, PLA2, or calmodulin. This inhibition of GABAB IPSCs through release of calcium from stores is a postsynaptic mechanism that may broadly reduce GIRK-dependent inhibition of many central neurons.

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“…There is evidence that chronic administration of L-Dopa increases prefrontal cortex dopamine and serum corticosterone (a stress-related hormone) [ 25 ] and could enhance aberrant signaling in the D1 pathway [ 24 ] in denervation states, which arguably could be the case in the presence of chronic antagonists or reward deficiency. There is also evidence of a profound serotonin-dopamine imbalance, following L-Dopa treatment [ 26 ]. Some manufacturers, despite FDA restrictions, have produced plant-based L-Dopa in the form of Velvet Bean (Mucuna pruriens) and studies have linked this to both psychosis and homicidal behavior [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

“Dopamine homeostasis” requires balanced polypharmacy: Issue with destructive, powerful dopamine agents to combat America’s drug epidemic

Blum

Gondré–Lewis

et al. 2017

J Syst Integr Neurosci

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The well-researched pro-dopamine regulator KB220 and variants result in increased functional connectivity in both animal and human brains, and prolonged neuroplasticity (brain cell repair) having been observed in rodents. Moreover, in addition to increased functional connectivity, recent studies show that KB220Z increases overall brain connectivity volume, enhances neuronal dopamine firing, and eliminates lucid dreams in humans over a prolonged period. An unprecedented number of clinical studies validating this patented nutrigenomic technology in re-balancing brain chemistry and optimizing dopamine sensitivity and function have been published. On another note, it is sad that unsuspecting consumers could be deceived and endangered by false promises of knock-off marketers with look- and- sound-alike products. Products containing ingredients having potential dangers (i.e., combinations of potent D2 agonists including L-Dopa and L-Theanine) threaten the credibility and reputation of validated, authentic, and ethical products. We encourage clinicians and neuroscientists to continue to embrace the concept of “dopamine homeostasis” and search for safe, effective, validated and authentic means to achieve a lifetime of recovery, instead of reverting to anti-dopaminergic agents doomed to fail in the war against the devastating drug epidemic, or promoting powerful D2 agonists that compromise needed balance.

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Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

Cited by 33 publications

References 46 publications

Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

Calcium Release from Stores Inhibits GIRK

“Dopamine homeostasis” requires balanced polypharmacy: Issue with destructive, powerful dopamine agents to combat America’s drug epidemic

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