Dorsal hippocampus plays a causal role in context-induced reinstatement of alcohol-seeking in rats

Felipe, Jaqueline Moreira; Palombo, Paola; P, Bianchi; Zaniboni, C.; Anesio, Augusto; Yokoyama, Thaís S.; Engi, Sheila A.; Carneiro-de-Oliveira, P.E.; Planeta, Cleópatra da Silva; Leão, Rodrigo M.; Cruz, Fábio C.

doi:10.1016/j.bbr.2020.112978

Cited by 14 publications

(6 citation statements)

References 89 publications

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“…Few studies have attempted to investigate the role of the hippocampus in the contextdriven reinstatement of ethanol-seeking behaviors. Correlative studies demonstrate that the reinstatement of ethanol seeking driven by the ethanol context is accompanied by increases in the transcription and protein synthesis of markers of neuronal activation in the hippocampus [47][48][49][50]. More notable is that the pharmacological inactivation of the hippocampus prevents the reinstatement of ethanol seeking triggered by ethanol context, indicating a direct role of the hippocampus in ethanol-context memories and motivation to seek ethanol [50].…”

Section: Discussionmentioning

confidence: 98%

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Nonoguchi,

Jin,

Narreddy

et al. 2023

IJMS

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Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor (CIE) and ethanol drinking (ED) procedure. During the last week of CIE, a subset of male and female TK rats was fed valcyte to ablate dividing progenitor cells and continued the diet until the end of this study. Following week six, all CIE rats experienced two weeks of forced abstinence from CIE-ED, after which they experienced relapse to drinking, extinction, and reinstatement of ethanol seeking sessions. CIE increased ED in female and male rats, with females having higher ethanol consumption during CIE and relapse sessions compared with males. In both sexes, valcyte reduced the levels of Ki-67-labeled progenitor cells in the subgranular zone of the dentate gyrus and did not alter the levels in the medial prefrontal cortex (mPFC). Valcyte increased ED during relapse, increased lever responses during extinction and, interestingly, enhanced latency to extinguish ethanol-seeking behaviors in males. Valcyte reduced the reinstatement of ethanol-seeking behaviors triggered by ethanol cues in females and males. Reduced seeking by valcyte was associated with the normalization of cytokines and chemokines in plasma isolated from trunk blood, indicating a role for progenitor cells in peripheral inflammatory responses. Reduced seeking by valcyte was associated with increases in tight junction protein claudin-5 and oligodendrogenesis in the dentate gyrus and reduction in microglial activity in the dentate gyrus and mPFC in females and males, demonstrating a role for progenitor cells in the dentate gyrus in dependence-induced endothelial and microglial dysfunction. These data suggest that progenitor cells born during withdrawal and abstinence from CIE in the dentate gyrus are aberrant and could play a role in strengthening ethanol memories triggered by ethanol cues via central and peripheral immune responses.

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Section: Discussionmentioning

confidence: 98%

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Nonoguchi,

Jin,

Narreddy

et al. 2023

IJMS

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“…However, as changes in mRNA do not necessarily reflect changes in protein ( Maier et al, 2009 ), follow up studies are needed to confirm that mRNA results translate to changes in protein expression. Because the hippocampus plays an important role in the induction of context-associated drug seeking in animal models of psychostimulants and opioids ( Taubenfeld et al, 2010 ; Bossert et al, 2016 ; Galinato et al, 2018 ; Noe et al, 2019 ; Felipe et al, 2021 ), it will be important to investigate context- and cue-induced in parallel to assess if similar or distinct molecular changes are associated with these behavioral phenomena. In addition, although we have discussed the molecular changes in terms of their facilitating oxycodone drug seeking behaviors, it is possible that these changes might have actually been consequences to lever pressing.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus

2021

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People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 h and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction analyses. Rats, given long-access (9 h per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 h per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6, and Grm8 subtypes of glutamate receptors after 31 days but not after 2 h of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

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“…In summary, we found that there were significant changes in the expression of several glutamate receptors in the hippocampus and that some of these changes correlated positively with increased oxycodone seeking within their same individual cages at WD30, a phenomenon that may reflect relapse potential in humans under similar conditions. Because the hippocampus plays an important role in the induction of context-associated drug seeking in animal models of psychostimulants and opioids [Bossert et al, 2016;Felipe et al, 2021;Galinato et al, 2018;Noe et al, 2019;Taubenfeld et al, 2010], it will be important to investigate context-and cue-induced in parallel to assess if similar or distinct molecular changes are associated with these behavioral phenomena. In addition, although we have discussed the molecular changes in terms of their facilitating oxycodone drug seeking behaviors, it is possible that these changes might have actually been consequences to lever pressing.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

Salisbury

Blackwood

Cadet

2020

Preprint

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People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6 and Grm8 subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

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Dorsal hippocampus plays a causal role in context-induced reinstatement of alcohol-seeking in rats

Cited by 14 publications

References 89 publications

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats

Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus

Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

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