Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice
Our study aims at comparing in C57/Bl male mice, the impact of repeated injections of baclofen (an agonist of GABAB receptor) or diazepam (a benzodiazepine acting through a positive allosteric modulation of GABAA receptor) administered during the alcohol-withdrawal period on hippocampus-dependent me...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.799225/full |
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| author | Henkous Nadia Martins Fabienne Christophe Pierard Mons Nicole Beracochea Daniel |
| author_facet | Henkous Nadia Martins Fabienne Christophe Pierard Mons Nicole Beracochea Daniel |
| author_sort | Henkous Nadia |
| collection | DOAJ |
| description | Our study aims at comparing in C57/Bl male mice, the impact of repeated injections of baclofen (an agonist of GABAB receptor) or diazepam (a benzodiazepine acting through a positive allosteric modulation of GABAA receptor) administered during the alcohol-withdrawal period on hippocampus-dependent memory impairments and brain regional glucocorticoid dysfunction after a short (1-week) or a long (4-week) abstinence. Hence, mice were submitted to a 6-month alcohol consumption (12%v/v) and were progressively withdrawn to water. Then, after a 1- or 4-weeks abstinence, they were submitted to a contextual memory task followed by measurements of corticosterone concentrations in the dorsal hippocampus (dHPC), the ventral hippocampus (vHPC) and the prefrontal cortex (PFC). Results showed that 1- and 4-week withdrawn mice exhibited a severe memory deficit and a significant abnormal rise of the test-induced increase of corticosterone (TICC) in the dHPC, as compared to water-controls or to mice still under alcohol consumption. Repeated daily systemic administrations of decreasing doses of diazepam (ranged from 0.5 to 0.12 mg/kg) or baclofen (ranged from 1.5 to 0.37 mg/kg) during the last 15 days of the withdrawal period, normalized both memory and TICC scores in the dHPC in 1-week withdrawn animals; in contrast, only baclofen-withdrawn mice showed both normal memory performance and TICC scores in the dHPC after a 4-week withdrawal period. In conclusion, the memory improvement observed in 4-week withdrawn mice administered with baclofen stem from the protracted normalization of glucocorticoid activity in the dHPC, a phenomenon encountered only transitorily in diazepam-treated withdrawn mice. |
| first_indexed | 2024-04-14T04:38:42Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-04-14T04:38:42Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-0f639cda2a0f407c85eaad0f7bfd4b6b2022-12-22T02:11:44ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402022-05-011310.3389/fpsyt.2022.799225799225Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in MiceHenkous Nadia0Martins Fabienne1Christophe Pierard2Mons Nicole3Beracochea Daniel4Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, CNRS UMR 5287, Pessac, FranceInstitut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, CNRS UMR 5287, Pessac, FranceInstitut de Recherche Biomédicale des Armées (IRBA), Place Général Valérie André, Brétigny-sur-Orge, FranceInstitut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, CNRS UMR 5287, Pessac, FranceInstitut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Université de Bordeaux, CNRS UMR 5287, Pessac, FranceOur study aims at comparing in C57/Bl male mice, the impact of repeated injections of baclofen (an agonist of GABAB receptor) or diazepam (a benzodiazepine acting through a positive allosteric modulation of GABAA receptor) administered during the alcohol-withdrawal period on hippocampus-dependent memory impairments and brain regional glucocorticoid dysfunction after a short (1-week) or a long (4-week) abstinence. Hence, mice were submitted to a 6-month alcohol consumption (12%v/v) and were progressively withdrawn to water. Then, after a 1- or 4-weeks abstinence, they were submitted to a contextual memory task followed by measurements of corticosterone concentrations in the dorsal hippocampus (dHPC), the ventral hippocampus (vHPC) and the prefrontal cortex (PFC). Results showed that 1- and 4-week withdrawn mice exhibited a severe memory deficit and a significant abnormal rise of the test-induced increase of corticosterone (TICC) in the dHPC, as compared to water-controls or to mice still under alcohol consumption. Repeated daily systemic administrations of decreasing doses of diazepam (ranged from 0.5 to 0.12 mg/kg) or baclofen (ranged from 1.5 to 0.37 mg/kg) during the last 15 days of the withdrawal period, normalized both memory and TICC scores in the dHPC in 1-week withdrawn animals; in contrast, only baclofen-withdrawn mice showed both normal memory performance and TICC scores in the dHPC after a 4-week withdrawal period. In conclusion, the memory improvement observed in 4-week withdrawn mice administered with baclofen stem from the protracted normalization of glucocorticoid activity in the dHPC, a phenomenon encountered only transitorily in diazepam-treated withdrawn mice.https://www.frontiersin.org/articles/10.3389/fpsyt.2022.799225/fullhippocampusprefrontal cortexethanolglucocorticoidsGABAmemory |
| spellingShingle | Henkous Nadia Martins Fabienne Christophe Pierard Mons Nicole Beracochea Daniel Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice Frontiers in Psychiatry hippocampus prefrontal cortex ethanol glucocorticoids GABA memory |
| title | Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice |
| title_full | Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice |
| title_fullStr | Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice |
| title_full_unstemmed | Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice |
| title_short | Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice |
| title_sort | preventive effects of baclofen but not diazepam on hippocampal memory and glucocorticoid alterations after prolonged alcohol withdrawal in mice |
| topic | hippocampus prefrontal cortex ethanol glucocorticoids GABA memory |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.799225/full |
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