Acute Effects of Lithium on Central Dopamine and Serotonin Activity Reflected by Inhibition of Prolactin and Growth Hormone Secretion in the Rat

Smythe, George A.; Brandstater, JF; Lazarus, L.

doi:10.1071/bi9790329

Cited by 11 publications

(7 citation statements)

References 14 publications

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“…Previous data reported that lithium treatment significantly inhibited both prolactin and GH secretion in the rat (Smythe et al 1979), in agreement with our findings. GH release is controlled by GHRH, somatostatin, and ghrelin (Anderson and Scanes 2012).…”

Section: Discussionsupporting

confidence: 96%

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Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Caberlotto

Carboni

Zanderigo

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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Glycogen synthase kinase (GSK3) is a constitutively active serine-threonine kinase associated to neurological and psychiatric disorders. GSK3 inhibition is considered a mediator of the efficacy of the mood-stabiliser lithium. This study aimed at comparing the central nervous system effect of lithium with the selective GSK3 inhibitors AZ1080 and compound A in biochemical, cellular, and behavioural tests. Collapsin response mediator protein 2 is a neuron-specific GSK3 substrate. Lithium, AZ1080, and compound A inhibited its phosphorylation in rat primary neurons with different pIC50. After systemic treatments with lithium or GSK3 inhibitors to assess specific functional responses, phosphorylation was unchanged in adult rat brain, while it was strongly inhibited by GSK3 inhibitors in pups, differently from lithium. Lithium may exert neurotrophic effect by increasing brain-derived neurotrophic factor (BDNF) levels: in the present experimental conditions, lithium exerted opposite effects on plasma BDNF levels compared to GSK3 inhibitors, suggesting this effect might not be necessarily mediated by GSK3 inhibition alone. While plasma thyroid-stimulating hormone and luteinising hormone were not affected by lithium, they were decreased by selective inhibitors. GH and prolactin displayed similar responses towards reduction. Follicle-stimulating hormone levels were not altered by treatments, whereas melatonin was specifically increased by AZ1080. Lithium impaired mouse spontaneous locomotion and decreased amphetamine-induced hyper-locomotion. AZ1080 had no effects on locomotion, while compound A reduced spontaneous locomotor activity without effects on amphetamine-induced hyper-locomotion. The present results indicate that a broad correlation between the effects of lithium and selective GSK3 inhibitors could not be devised, suggesting alternative mechanisms, whereas overlapping results could be obtained in specific assays.

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Section: Discussionsupporting

confidence: 96%

“…Available data suggested that lithium administration affects blood levels of multiple hormones (Banerji et al 1983;Seggie et al 1985;Smythe et al 1979). Interestingly, this approach highlighted a divergent panel of hormonal alterations due to either lithium or more selective GSK3 inhibitor treatments.…”

Section: Discussionmentioning

confidence: 96%

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Caberlotto

Carboni

Zanderigo

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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“…BPD patients undergoing lithium treatment exhibited decreased prolactin levels [25,52]. Moreover, the administration of lithium significantly inhibited prolactin secretion in rats [53]. Intriguingly, lithium attenuated DGKη-deficient-induced mania-like phenotypes as well [21].…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain

Komenoi

Suzuki

Asami

et al. 2019

Biochemistry and Biophysics Reports

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We have revealed that diacylglycerol kinase η (DGKη)-knockout (KO) mice display bipolar disorder (BPD) remedy-sensitive mania-like behaviors. However, the molecular mechanisms causing the mania-like abnormal behaviors remain unclear. In the present study, microarray analysis was performed to determine global changes in gene expression in the DGKη-KO mouse brain. We found that the DGKη-KO brain had 43 differentially expressed genes and the following five affected biological pathways: “neuroactive ligand-receptor interaction”, “transcription by RNA polymerase II”, “cytosolic calcium ion concentration”, “Jak-STAT signaling pathway” and “ERK1/2 cascade”. Interestingly, mRNA levels of prolactin and growth hormone, which are augmented in BPD patients and model animals, were most strongly increased. Notably, all five biological pathways include at least one gene among prolactin, growth hormone, forkhead box P3, glucagon-like peptide 1 receptor and interleukin 1β, which were previously implicated in BPD. Consistent with the microarray data, phosphorylated ERK1/2 levels were decreased in the DGKη-KO brain. Microarray analysis showed that the expression levels of several glycerolipid metabolism-related genes were also changed. Liquid chromatography-mass spectrometry revealed that several polyunsaturated fatty acid (PUFA)-containing phosphatidic acid (PA) molecular species were significantly decreased as a result of DGKη deficiency, suggesting that the decrease affects PUFA metabolism. Intriguingly, the PUFA-containing lysoPA species were markedly decreased in DGKη-KO mouse blood. Taken together, our study provides not only key broad knowledge to gain novel insights into the underlying mechanisms for the mania-like behaviors but also information for developing BPD diagnostics.

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“…Serotonin promotes anterograde movement towards axons and dendritic terminals while dopamine inhibits mitochondrial transport [14]. Mitochondrial trafficking has just now been linked to changes in the activity of neurons modulated by serotonin and dopamine [46], [47], [48]. Therefore, our hypothesis regarding the effect of mood stabilizers (and antipsychotics) extends beyond the traditional mode of action of these drugs on receptor binding and synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

New Model of Action for Mood Stabilizers: Phosphoproteome from Rat Pre-Frontal Cortex Synaptoneurosomal Preparations

et al. 2013

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BackgroundMitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level.HypothesisMitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement.MethodsSynaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry.ResultsLithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation.ConclusionsMood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights regarding clinical treatment and the mode of action of these drugs.

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Acute Effects of Lithium on Central Dopamine and Serotonin Activity Reflected by Inhibition of Prolactin and Growth Hormone Secretion in the Rat

Cited by 11 publications

References 14 publications

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain

New Model of Action for Mood Stabilizers: Phosphoproteome from Rat Pre-Frontal Cortex Synaptoneurosomal Preparations

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