Modulatory Effects of Ketamine and Lamotrigine on Cognition: Emotion Interaction in the Brain

Gärtner, Matti; Weigand, Anne; Keicher, Christian; Meiering, Marvin Sören; Weigner, David; Carstens, Luisa; Hertrampf, R; Beckmann, Christian F.; Mennes, Maarten; Wunder, Andreas; Grimm, Simone

doi:10.1159/000528315

Cited by 6 publications

(4 citation statements)

References 89 publications

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“…Both, the PK and LK groups had increased scores on the DSS scale and on the subscales of the 5D-ASC questionnaire. Detailed behavioral and demographic results are provided in Supplementary Table 1 and in our previous publication [28].…”

Section: Resultsmentioning

confidence: 99%

“…Expected effect sizes were based on previous reports [39]. More details about the design and procedures are provided by Gärtner et al [28].…”

Section: Experimental Design and Proceduresmentioning

confidence: 99%

“…Utilizing techniques to modulate glutamate transmission can offer additional insights into the mechanisms of action of ketamine. Accordingly, previous studies have demonstrated that the acute effects of ketamine on brain activity [7,8,28] and connectivity [29] were attenuated by lamotrigine, an anticonvulsant drug that inhibits glutamate release [30]. Attenuated dissociative symptoms [7,31] underscored that the effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine.…”

Section: Introductionmentioning

confidence: 99%

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Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex

Gärtner,

Weigand,

Meiering

et al. 2024

Transl Psychiatry

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Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine’s antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes. Furthermore, the assessment of trait negative emotionality holds promise to link findings in healthy participants to potential AD mechanisms of ketamine. In this double-blind, placebo-controlled, randomized, single dose, parallel-group study, we collected resting-state fMRI data before, during, and 24 h after ketamine administration in a sample of 75 healthy male and female participants who were randomly allocated to one of three treatment conditions (ketamine, ketamine with lamotrigine pre- treatment, placebo). Spontaneous brain activity was extracted from two ventral and one dorsal subregions of the ACC. Our results showed activity decreases during the administration of ketamine in all three ACC subregions. However, only in the ventral subregions of the ACC this effect was attenuated by lamotrigine. 24 h after administration, ACC activity returned to baseline levels, but group differences were observed between the lamotrigine and the ketamine group. Trait negative emotionality was closely linked to activity changes in the subgenual ACC after ketamine administration. These results contribute to an understanding of the functional significance of ketamine effects in different subregions of the ACC by combining an approach to modulate glutamate release with the assessment of multiple timepoints and associations with trait negative emotionality in healthy participants.

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Section: Resultsmentioning

confidence: 99%

“…Expected effect sizes were based on previous reports [39]. More details about the design and procedures are provided by Gärtner et al [28].…”

Section: Experimental Design and Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex

Gärtner,

Weigand,

Meiering

et al. 2024

Transl Psychiatry

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“…We used PDC (a glutamate transporter inhibitor, known to increase synaptic glutamate by inhibiting the uptake of glutamate) and lamotrigine (inhibits glutamate release). Lamotrigine is a broad-spectrum anticonvulsant and its downstream effects on neuronal function include inhibition of glutamate release (Bacher and Zornow, 1997; Anand et al ., 2000; Makatsori et al ., 2004; Large et al ., 2005; Gärtner et al ., 2023) by inhibiting voltage-sensitive sodium channels (Messenheimer, 1995). We found that the stimulation of glutamatergic neurons in LHb via local infusion of PDC resulted in a significant reduction in TH-ir and consequently CPP score.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological evaluation of lateral habenula and rostromedial tegmental nucleus in the expression of ethanol-induced place preference

Gakare

Ugale

2023

Behavioural Pharmacology

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Although ethanol administration produces a range of physiological effects, the rewarding aspect associated with its consumption is a major contributory factor to its abuse liability. Recently, lateral habenula (LHb) has been shown to be engaged by both rewarding and aversive stimuli. Its major glutamatergic output, the fasciculus retroflexus, projects to the rostromedial tegmental nucleus (RMTg) and controls the activity of the ventral tegmental area (VTA) dopaminergic system to promote reward circuitry. While several attempts have been made to understand the relationship between LHb and addiction, there is still a lack of knowledge in relation to ethanol addiction. In the present study, by pharmacologically exacerbating or inhibiting the LHb or RMTg neuronal activity during a post-conditioning test, we investigated the role of LHb-RMTg fasciculus retroflexus in ethanol-induced reward behavior using the conditioned place preference (CPP) test. We found that activation of LHb glutamatergic system by intra-LHb administration of l-trans-2,4-pyrrolidine dicarboxylate (PDC) (glutamate transporter inhibitor) significantly decreased CPP score; on the contrary, lamotrigine (inhibits glutamate release) significantly increased CPP score and showed a rewarding effect in CPP. Instead, intra-RMTg administration of muscimol (GABAA receptor agonist) significantly increased CPP score, whereas bicuculline (GABAA antagonist) treatment decreased CPP score. In immunohistochemistry, we found that PDC administration significantly decreased, whereas lamotrigine treatment significantly increased tyrosine hydroxylase immunoreactivity (TH-ir) in VTA and nucleus accumbens (NAc). Furthermore, while intra-RMTg administration of muscimol increased, the bicuculline treatment significantly decreased the TH-ir in VTA and NAc. Together, our behavioral and immunohistochemical results signify the role of LHb and RMTg in the expression of ethanol-conditioned reward behavior.

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Cognitive and Emotional Effect of a Multi-species Probiotic Containing Lactobacillus rhamnosus and Bifidobacterium lactis in Healthy Older Adults: A Double‐Blind Randomized Placebo‐Controlled Crossover Trial

Ruiz-Gonzalez,

Cardona,

Rueda-Ruzafa

et al. 2024

Probiotics & Antimicro. Prot.

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As the population ages, cognitive decline becomes more common. Strategies targeting the gut-brain axis using probiotics are emerging to achieve improvements in neuropsychiatric and neurological disorders. However, the beneficial role of probiotics on brain function in healthy older adults remains unclear. Our aim was to evaluate a multi-species probiotic formulation as a therapeutic approach to reduce emotional and cognitive decline associated with aging in healthy adults. A randomized double-blind placebo-controlled crossover trial was conducted. The study involved a 10-week intervention where participants consumed the assigned probiotic product daily, followed by a 4-week washout period before the second condition started. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Psychological Experiments Construction Language Test Battery. At the emotional level, the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used. Thirty-three participants, recruited between July 2020 and April 2022, ingested a multispecies probiotic (Lactobacillus rhamnosus and Bifidobacterium lactis). After the intervention, noticeable enhancements were observed in cognitive function (mean difference 1.90, 95% CI 1.09 to 2.70, p < 0.005), memory (mean difference 4.60, 95% CI 2.91 to 6.29, p < 0.005) by MMSE and digit task, and depressive symptoms (mean difference 4.09, 95% CI 1.70 to 6.48, p < 0.005) by BDI. Furthermore, there were significant improvements observed in planning and problem-solving skills, selective attention, cognitive flexibility, impulsivity, and inhibitory ability. Probiotics administration improved cognitive and emotional function in older adults. Limited research supports this, requiring more scientific evidence for probiotics as an effective therapy for cognitive decline. This study has been prospectively registered at ClinicalTrials.gov (NCT04828421; 2020/July/17).

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Modulatory Effects of Ketamine and Lamotrigine on Cognition: Emotion Interaction in the Brain

Cited by 6 publications

References 89 publications

Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex

Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex

Pharmacological evaluation of lateral habenula and rostromedial tegmental nucleus in the expression of ethanol-induced place preference

Cognitive and Emotional Effect of a Multi-species Probiotic Containing Lactobacillus rhamnosus and Bifidobacterium lactis in Healthy Older Adults: A Double‐Blind Randomized Placebo‐Controlled Crossover Trial

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