Hippocampal glutamate is increased and associated with risky drinking in young adults with major depression

Hermens, Daniel F.; Chitty, Kate M.; Lee, Rico Sc; Tickell, Ashleigh M.; Haber, Paul S.; Naismith, Sharon L.; Hickie, Ian B.; Lagopoulos, Jim

doi:10.1016/j.jad.2015.07.009

Cited by 29 publications

(16 citation statements)

References 24 publications

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“…Repeated 2–3.4 g/kg alcohol injections increase accumbal and hippocampal glutamate compared with water-injected animals 1, 87, 88 . This confirms a study in which young adults with depression had a positive correlation between the level of alcohol use and glutamate in the hippocampus 89 .…”

Section: Episodic Drinking Through Binges and Relapsesupporting

confidence: 89%

Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective

2017

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Glutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal behavior protocols can be used to assess these different drinking levels, including two-bottle choice, operant self-administration, drinking in the dark, the alcohol deprivation effect, intermittent access to alcohol, and chronic intermittent ethanol vapor inhalation. Importantly, these methods are not limited to a specific category, since they can be interchanged to assess different states in the development from low to heavy drinking. We encourage a circuit-based perspective beyond the classic mesolimbic-centric view, as multiple structures are dynamically engaged during the transition from positive- to negative-related reinforcement to drive alcohol drinking. During this shift from lower-level alcohol drinking to heavy alcohol use, there appears to be a shift from metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate receptor-related processes. Despite high efficacy of the glutamate-related pharmaceutical acamprosate in animal models of drinking, it is ineffective as treatment in the clinic. Therefore, research needs to focus on other promising glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms or both.

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Section: Episodic Drinking Through Binges and Relapsesupporting

confidence: 89%

Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective

2017

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“…QUIN induces increased glutamate in the synaptic cleft and the presynaptic membrane via promoting synaptosomal glutamate release (Tavares et al 2005). Moreover, young people with depression have significantly higher glutamate levels in the HIPPO (Hermens et al 2015), which is thought to induce abnormal cognitive behavior (Potter et al 2010). Here, significant downregulation of the HIPPO KYNA level was observed in the stress-susceptible mice with reduced locomotor activity.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, young people with depression have significantly higher glutamate levels in the HIPPO (Hermens et al . ), which is thought to induce abnormal cognitive behavior (Potter et al . ).…”

Section: Discussionmentioning

confidence: 99%

Validation of the targeted metabolomic pathway in the hippocampus and comparative analysis with the prefrontal cortex of social defeat model mice

Chen

et al. 2019

Journal of Neurochemistry

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The proportion of major depressive disorder (MDD) patients around the world has increased remarkably. Although many studies of MDD have been conducted based on classic hypotheses, like alteration of the hypothalamic–pituitary–adrenal axis or monoamine neurotransmitters, the mechanisms underlying MDD remain unclear. Aiming to further investigate the mechanisms of MDD, liquid chromatography–tandem mass spectrometry was employed to measure target metabolites in the hippocampus (HIPPO) of chronic social defeat stress model mice. Compared with control mice, stress‐susceptible mice showed a reduction of 5‐hydroxyindoleacetic acid and kynurenic acid in the tryptophan pathway, and an increased level of dopamine in the catecholamine pathway, while stress‐resilient mice displayed a reduction of 5‐hydroxytryptamine in the tryptophan pathway. The altered levels of key molecules related to the tryptophan or dopamine metabolic pathways were validated by real‐time quantitative polymerase chain reaction or western blotting. Comparative analysis with previous targeted metabolomics results in the prefrontal cortex (PFC) of chronic social defeat stress mice revealed that the altered metabolites manifested in specific brain areas, and only the dopamine metabolic pathway was perturbed in both the HIPPO and PFC after stress. Additionally, correlation analysis validated that levels of kynurenic acid in the HIPPO, along with glutamic acid, L‐3, 4‐dihydroxyphenylalanine, and vanillylmandelic acid in the PFC, were correlated with depression‐like behaviors. This study provides a unique perspective on the potential molecular mechanisms of stress susceptibility and stress resilience.

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“…Present studies showed that chronic intake of both drugs leads to brain oxidative stress and neuroinflammation, as shown by an elevated hippocampal GSSG/GSH ratio and astrocyte immunoreactivity, respectively. The hippocampus is the brain area most pathologically affected by chronic EtOH intake (Franke et al., ; Walker et al., ), which in humans has been proposed to be responsible for the loss of control over drinking and severe intoxication (see Crews, ; Hermens et al., ). For nicotine, hippocampal function is responsible for the associative‐learned drug cues that perpetuate drug intake (Davis and Gould, ).…”

Section: Discussionmentioning

confidence: 99%

Commonality of Ethanol and Nicotine Reinforcement and Relapse in Wistar‐Derived UChB Rats: Inhibition by N‐Acetylcysteine

Quintanilla

Morales

Ezquer

et al. 2018

Alcoholism Clin & Exp Res

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Hippocampal glutamate is increased and associated with risky drinking in young adults with major depression

Cited by 29 publications

References 24 publications

Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective

Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective

Validation of the targeted metabolomic pathway in the hippocampus and comparative analysis with the prefrontal cortex of social defeat model mice

Commonality of Ethanol and Nicotine Reinforcement and Relapse in Wistar‐Derived UChB Rats: Inhibition by N‐Acetylcysteine

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