Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood

García-Cabrerizo, Rubén; Keller, Benjamin; García-Fuster, M. Julia

doi:10.1016/j.neuroscience.2015.07.040

Cited by 32 publications

(31 citation statements)

References 63 publications

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“…Videos were then analysed to obtain the baseline time spent immobile for each rat on PND 29 (Behavioral Tracker software, CA, USA). Following three days of rest, groups of rats were treated daily for seven days (PNDs 33–39) with saline (0.9% NaCl, 1 mL/kg, i.p., n =21) and cocaine (15 mg/kg, i.p., n =23), as previously described (see García-Cabrerizo et al, 2015 for the specific age-window of adolescent vulnerability; see also García-Fuster et al, 2017b for long-term effects in adulthood following the same experimental procedure in adolescence). This same paradigm of cocaine administration at this specific window of exposure induced behavioural psychomotor sensitization (see Parsegian et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

“…In this context, the present study aimed at extending prior knowledge on the effects of cocaine exposure during adolescence on negative affect in adulthood. Particularly, the present study is a follow-up of a recent paper from our research group (García-Cabrerizo et al, 2015) in which cocaine exposure (15 mg/kg per day, intraperitoneally (i.p. ), seven or 14 days) administered during early-mid adolescence (postnatal days (PNDs) 33-39 or PNDs 33-46) was not able to induce long-term effects on behavioural despair in adulthood.…”

Section: Introductionmentioning

confidence: 93%

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Adolescent cocaine exposure enhanced negative affect following drug re-exposure in adult rats: Attenuation of c-Fos activation

García-Cabrerizo

García-Fuster

2018

J Psychopharmacol

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Background: The goal of the present study was to utilize the adolescent drug experience as an emerging vulnerability factor for developing psychiatric comorbidities in adulthood that could, in turn, help to elucidate and/or hypothesize possible mechanisms contributing to higher relapse rates. Outcomes: The current results showed that adolescent cocaine exposure (15 mg/kg, intraperitoneally, seven days) during early–mid adolescence (postnatal days 33–39) enhanced negative affect in adulthood, by increasing behavioral despair following drug re-exposure and by increasing anhedonia. Thus, these behavioral data provided a good model to further ascertain the long-term cellular and molecular adaptations that might take place in the brain in response to adolescent cocaine exposure as well as the impact of drug re-exposure in adulthood. In this regard, the results showed that adolescent cocaine exposure did not modulate cell proliferation (Ki-67+ cells) or c-Fos protein activation in the dentate gyrus region of the hippocampus, but attenuated c-Fos activation in the dorsal striatum. Conclusions: These results proved that a history of cocaine exposure during adolescence increased the vulnerability to induce negative affect (i.e. emergence of psychiatric comorbidity) in adulthood while it decreased neuronal activation in the dorsal striatum. Interestingly, these effects were only observed following cocaine re-exposure in adulthood, suggesting that avoiding drug contact in adulthood could prevent the long-term negative effects induced by adolescent cocaine.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Adolescent cocaine exposure enhanced negative affect following drug re-exposure in adult rats: Attenuation of c-Fos activation

García-Cabrerizo

García-Fuster

2018

J Psychopharmacol

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“…Moreover, a prior study already showed a region-specific FADD regulation following repeated drug administration, with specific effects observed selectively in the hippocampus as compared to other brain regions (e.g. prefrontal cortex, see García-Cabrerizo et al, 2015). Additionally, this latter study also showed, in line with the present results, that while FADD was regulated in the hippocampus following repeated drug administration, p-FADD was not (García-Cabrerizo et al, 2015).…”

Section: Discussionmentioning

confidence: 95%

Repeated treatment with the α2-adrenoceptor agonist UK-14304 improves cognitive performance in middle-age rats: Role of hippocampal Fas-associated death domain

et al. 2017

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The cell fate regulator Fas-associated death domain (FADD) balances cell death with non-apoptotic actions via its phosphorylated form. A recent study associated loss of cortical FADD with cognitive decline and increased risk of clinical dementia. Since the activation of cortical α-adrenoceptors improved memory deficits in various animal models of working memory loss, the present study evaluated whether UK-14304, an α-adrenoceptor agonist known to acutely regulate brain FADD forms, would improve cognitive function in middle-aged rats. Sprague-Dawley rats were treated with UK-14304 (0.3 or 1 mg/kg) or saline (1 mL/kg) for seven days. Cognitive performance was evaluated in the eight-arm radial maze. FADD protein content was measured in the prefrontal cortex and hippocampus by Western blot analysis. The results showed that UK-14304 (1 mg/kg) improved cognitive performance (less time: -310±45 s, p=0.025 and fewer errors: -2.75±1.06, p=0.043 to complete the maze) and increased FADD selectively in the hippocampus (+35±11%, p=0.029). Interestingly, hippocampal FADD content negatively correlated with the time ( r=-0.651, p<0.01) needed to complete the maze. Thus, better cognitive scores were associated with higher FADD hippocampal content. These results support a role for α-adrenoceptors in ameliorating cognition and suggest FADD protein content as a possible correlate for cognitive performance.

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“…Four days later, rats began a once daily regimen of either systemic cocaine (15 mg/kg) or saline that lasted for 7 consecutive days (PND 33–39). This drug regimen was previously shown to induce psychomotor sensitization in adult outbred (Gosnell 2005) and bHR rats (García-Fuster et al 2010), and to impact brain markers in adulthood when given at this time-window during early-mid adolescence (see García-Cabrerizo et al 2015; García-Cabrerizo and García-Fuster 2016). …”

Section: Methodsmentioning

confidence: 99%

“…The number of immunostained positive cells was counted in every 8 th section throughout the septo-temporal extent of the hippocampus (−1.72 to −6.80 mm from Bregma) using a Leica DMR light microscope with a 63× oil objective lens in order to focus through the thickness of the section (30 µm). For each rat the total number of proliferating (Ki-67+) or surviving (BrdU+) cells counted in the dentate gyrus was expressed in relation to the overall quantified area (mm 2 ) (Amrein et al 2011; García-Cabrerizo et al 2015), which was measured using a densitometer (GS-800 Imaging Calibrated densitometer, BioRad).…”

Section: Methodsmentioning

confidence: 99%

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

et al. 2017

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Rationale Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. Objectives We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. Methods bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Results Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.

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Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood

Cited by 32 publications

References 63 publications

Adolescent cocaine exposure enhanced negative affect following drug re-exposure in adult rats: Attenuation of c-Fos activation

Adolescent cocaine exposure enhanced negative affect following drug re-exposure in adult rats: Attenuation of c-Fos activation

Repeated treatment with the α2-adrenoceptor agonist UK-14304 improves cognitive performance in middle-age rats: Role of hippocampal Fas-associated death domain

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

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