Task-dependent effects of the antidepressant/antipanic drug phenelzine on memory

Parent, Marise B.; Habib, Marie K.; Baker, Glen B.

doi:10.1007/s002130050890

Cited by 19 publications

(4 citation statements)

References 50 publications

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“…Zebrafish co-treated with L1 mimetic spent more time in the novel arm in comparison to the PQ-treated fish when their response to novelty was evaluated in the T-maze task, indicating an improvement of acquisition and consolidation of spatial memory. These findings are supported by the literature highlighting the improvement of learning and memory by PS and TC (Parent et al, 1999;Murakami et al, 2000;Yuede et al, 2007;Simpson et al, 2012). The improvement in the motor and non-motor deficits encouraged us to assess the neurochemical modifications upon co-treatment with PS or TC.…”

Section: Discussionsupporting

confidence: 76%

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish

et al. 2020

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Besides several endogenous elements, exogenous factors, including exposure to pesticides, have been recognized as putative factors contributing to the onset and development of neurodegenerative diseases, including Parkinson's disease (PD). Considering the availability, success rate, and limitations associated with the current arsenals to fight PD, there is an unmet need for novel therapeutic interventions. Therefore, based on the previously reported beneficial functions of the L1 cell adhesion molecule, we hypothesized that L1 mimetic compounds may serve to neutralize neurotoxicity triggered by the pesticide paraquat (PQ). In this study, we attempt to use PQ for inducing PD-like pathology and the L1 mimetic compounds phenelzine sulfate (PS) and tacrine (TC) as potential candidates for the amelioration of PD symptoms using zebrafish as a model system. Administration of PQ together with the L1 mimetic compounds PS or TC (250 nM) improved survival of zebrafish larvae, protected them from locomotor deficits, and increased their sensorimotor reflexes. Moreover, application of PQ together with PS (500 nM) or TC (1000 nM) in adult zebrafish counteracted PQ-induced toxicity, maintaining normal locomotor functions and spatial memory in an open field and T-maze task, respectively. Both L1 mimetic compounds prevented reduction in tyrosine hydroxylase and dopamine levels, reduced reactive oxygen species (ROS) generation, protected against impairment of mitochondrial viability, improved the antioxidant enzyme system, and prevented a decrease in ATP levels. Altogether, our findings highlight the beneficial functions of the agonistic L1 mimetics PS and TC by improving several vital cell functions against PQ-triggered neurotoxicity.

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Section: Discussionsupporting

confidence: 76%

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish

et al. 2020

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“…Chronic treatment with the tricyclic antidepressant amitriptyline, which inhibits 5HT and noradrenaline reuptake, enhances spatial learning in the water maze in young rats and prevents the age‐induced impairment observed in this task, possibly by reducing anxiety levels (Yau et al ., 1995, 2002). Conversely, however, the acute administration of the monoamine oxidase inhibitor phenelzine increases retention in an inhibitory avoidance task, but increases escape latencies and path lengths in the Morris water maze (Parent et al ., 1999). In clinical studies, tricyclic antidepressants have been shown to bring about deficits in working memory (Amado‐Boccara et al ., 1995; Caldeira de Carvalho et al ., 2002), while selective 5HT and noradrenaline reuptake inhibitors have little effect on memory (Siepmann et al ., 2001; Cassano et al ., 2002).…”

Section: Discussionmentioning

confidence: 99%

Increased neurogenesis and brain‐derived neurotrophic factor in neurokinin‐1 receptor gene knockout mice

Morcuende

Gadd

Peters³

et al. 2003

Eur J of Neuroscience

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It has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long-term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin-1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin-1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin-1 receptor knockout mice. Neurogenesis can be increased in wild-type but not neurokinin-1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain-derived neurotrophic factor are also two-fold higher in neurokinin-1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus-dependent learning and memory but found no clear enhancement in neurokinin-1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain-derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain-derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy.

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“…The effect of phenelzine is an elevation of brain levels of biogenic amines, including alanine and GABA [118][119][120]. In turn, glutamine levels are decreased [119], and, since alanine is an inhibitor of glutamine synthase [121], it may be postulated that its accumulation, conceivably due at least in part to AGXT inhibition, may induce a secondary reduction in brain glutamine levels [122].…”

Section: Alanine Aminotransferasementioning

confidence: 99%

Pyridoxal 5-Phosphate Enzymes as Targets for Therapeutic Agents

Amadasi¹,

Bertoldi²,

Contestabile³

et al. 2007

CMC

178

157

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The vitamin B(6)-derived pyridoxal 5'-phosphate (PLP) is the cofactor of enzymes catalyzing a large variety of chemical reactions mainly involved in amino acid metabolism. These enzymes have been divided in five families and fold types on the basis of evolutionary relationships and protein structural organization. Almost 1.5% of all genes in prokaryotes code for PLP-dependent enzymes, whereas the percentage is substantially lower in eukaryotes. Although about 4% of enzyme-catalyzed reactions catalogued by the Enzyme Commission are PLP-dependent, only a few enzymes are targets of approved drugs and about twenty are recognised as potential targets for drugs or herbicides. PLP-dependent enzymes for which there are already commercially available drugs are DOPA decarboxylase (involved in the Parkinson disease), GABA aminotransferase (epilepsy), serine hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African sleeping sickness and, potentially, tumors), alanine racemase (antibacterial agents), and human cytosolic branched-chain aminotransferase (pathological states associated to the GABA/glutamate equilibrium concentrations). Within each family or metabolic pathway, the enzymes for which drugs have been already approved for clinical use are discussed first, reporting the enzyme structure, the catalytic mechanism, the mechanism of enzyme inactivation or modulation by substrate-like or transition state-like drugs, and on-going research for increasing specificity and decreasing side-effects. Then, PLP-dependent enzymes that have been recently characterized and proposed as drug targets are reported. Finally, the relevance of recent genomic analysis of PLP-dependent enzymes for the selection of drug targets is discussed.

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Task-dependent effects of the antidepressant/antipanic drug phenelzine on memory

Cited by 19 publications

References 50 publications

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish

Increased neurogenesis and brain‐derived neurotrophic factor in neurokinin‐1 receptor gene knockout mice

Pyridoxal 5-Phosphate Enzymes as Targets for Therapeutic Agents

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