Modelling Differential Vulnerability to Substance Use Disorder in Rodents: Neurobiological Mechanisms

Jupp, Bianca; Jones, Jolyon A.; Dalley, Jeffrey W.

doi:10.1007/164_2019_300

Cited by 6 publications

(8 citation statements)

References 228 publications

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“…Clinical studies show that cocaine addiction includes poor inhibitory control for goal-directed behaviour in the frontal cortical regions, evidencing an impulse control disorder which induces drug craving (Barrós-Loscertales et al 2019). In line with this, preclinical studies demonstrated that increased impulsivity predicts predisposition for drug use to evolve towards drug abuse (Jupp et al 2020).…”

Section: Introductionmentioning

confidence: 82%

“…Impulsivity is a major personality and temperament dimension consisting of maladaptive behaviour and characterized by poorly conceived, prematurely expressed, unduly risky, or inappropriate actions often resulting in undesirable consequences (Granö et al 2007;Dent and Isles 2014;Dalley and Ersche 2019). Therefore, this personality trait can increase predisposition to suffer drug addiction (Nicholls et al 2014;Rømer Thomsen et al 2018;Adams et al 2019;Butelman et al 2019;Jupp et al 2020) and other psychiatric disorders like major depressive disorder (MDD) (Dent and Isles 2014;Dalley and Ersche 2019). Depression is the most common psychological disorder affecting more than 264 million people worldwide (James et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Cocaine-seeking behaviour is differentially expressed in male and female mice exposed to maternal separation and is associated with alterations in AMPA receptors subunits in the medial prefrontal cortex.

Castro‐Zavala

Martín‐Sánchez

Montalvo-Martínez

et al. 2021

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Impulsivity is a key trait in the diagnosis of major depressive disorder (MDD) and substance use disorder (SUD). MDD is a chronic illness characterized by sadness, insomnia, and loss of interest. SUD is a chronic and relapsing disorder characterized by the consumption of drugs despite their negative consequences. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that increased impulsivity predicts predisposition to acquire cocaine self-administration (SA) behaviour with an increased cocaine-intake. Moreover, early-life stress represents a vulnerability factor to develop depressive disorders and drug addiction. Maternal separation with early weaning (MSEW) is an animal model that allows examining the impact of early-life stress on cocaine abuse. In this study, we aimed to explore changes in MSEW-induced impulsivity to determine potential associations between depression-like and cocaineseeking behaviours in male and female mice. We also evaluated possible alterations in the AMPA receptors (AMPArs) composition and glutamatergic neurotransmission. We exposed mice to MSEW and the behavioural tests were performed during adulthood. Moreover, GluA1, GluA2 mRNA and protein expression were evaluated in the medial Prefrontal Cortex (mPFC). Results showed higher impulsive cocaine-seeking in females, independently the MSEW, as well as an increase in GluA1 and GluA2 protein expression.Moreover, MSEW induced downregulation of Gria2 and increased the GluA1/GluA2 ratio, only in male mice. In conclusion, female mice expressed higher mPFC glutamatergic function, which potentiated their impulsivity during cocaine SA. Also, data indicated that MSEW alters glutamatergic function in mPFC of male mice, increasing the glutamatergic excitability.

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Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Cocaine-seeking behaviour is differentially expressed in male and female mice exposed to maternal separation and is associated with alterations in AMPA receptors subunits in the medial prefrontal cortex.

Castro‐Zavala

Martín‐Sánchez

Montalvo-Martínez

et al. 2021

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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show abstract

“…One of the core traits shown by rat strains with differential vulnerability to drug addiction is the capacity to self-administer more drug than other rat strains 1,4,39,40 . According to this, drug intake is very high in some vulnerable animals and very low in other resistant ones 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Addiction vulnerability is the individual's risk of developing an addiction during their lifetime. Clinical and preclinical studies have shown that among the biological factors involved in this disorder, genetic variability plays an important role in humans [1][2][3][4] , accounting for at least 40-60% of the variation in vulnerability to drug dependence 5 . In this regard, the use of inbred rats has proven to be a valuable tool for identifying differences in vulnerability to drug addiction.…”

Section: Introductionmentioning

confidence: 99%

Neuroimaging Reveals Distinct Brain Glucose Metabolism Patterns Associated with Morphine Consumption in Two Inbreed Rat Models

Soto-Montenegro

García

Lamanna-Rama

et al. 2021

Preprint

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Addiction vulnerability is the individual's risk of developing an addiction during their lifetime. A challenge in the neurobiology of drug addiction is understanding why some people become addicted to drugs. Here, we used positron emission tomography (PET) and statistical parametric mapping (SPM) to evaluate changes in brain glucose metabolism in response to chronic morphine self-administration (MSA) in two rat strains with different vulnerability to drug abuse, Lewis (LEW) and Fischer 344 (F344). Four groups of animals were trained to self-administer morphine or saline for 15 days. 2-deoxy-2-[18F]-fluoro-D-glucose (FDG)-PET studies were performed on the last day of MSA (acquisition phase) and after 15 days of withdrawal. PET data were analyzed using SPM12. LEW-animals self-administered more morphine injections per session than F344-animals. We found significant brain metabolic differences between LEW and F344 strains in the cortex, hypothalamus, brainstem, and cerebellum. In addition, the different brain metabolic patterns observed after the MSA study between these rat strains indicate differences in the efficiency of neural substrates to translate the drug effects, which could explain the differences in predisposition to morphine abuse between one individual and another. These findings have important implications for the use of these rat strains in translational morphine and opiate research.

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“…Addiction vulnerability is the individual's risk of developing an addiction during their lifetime. Clinical and preclinical studies have shown that among the biological factors involved in this disorder, genetic variability plays an important role in humans 1 – 4 , accounting for at least 40–60% of the variation in vulnerability to drug dependence 5 . In this regard, the use of inbred rats has proven to be a valuable tool for identifying differences in vulnerability to drug addiction.…”

Section: Introductionmentioning

confidence: 99%

Neuroimaging reveals distinct brain glucose metabolism patterns associated with morphine consumption in Lewis and Fischer 344 rat strains

Soto-Montenegro

García-Vázquez

Lamanna-Rama

et al. 2022

Sci Rep

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Vulnerability to addiction may be given by the individual's risk of developing an addiction during their lifetime. A challenge in the neurobiology of drug addiction is understanding why some people become addicted to drugs. Here, we used positron emission tomography (PET) and statistical parametric mapping (SPM) to evaluate changes in brain glucose metabolism in response to chronic morphine self-administration (MSA) in two rat strains with different vulnerability to drug abuse, Lewis (LEW) and Fischer 344 (F344). Four groups of animals were trained to self-administer morphine or saline for 15 days. 2-deoxy-2-[18F]-fluoro-d-glucose (FDG)-PET studies were performed on the last day of MSA (acquisition phase) and after 15 days of withdrawal. PET data were analyzed using SPM12. LEW-animals self-administered more morphine injections per session than F344-animals. We found significant brain metabolic differences between LEW and F344 strains in the cortex, hypothalamus, brainstem, and cerebellum. In addition, the different brain metabolic patterns observed after the MSA study between these rat strains indicate differences in the efficiency of neural substrates to translate the drug effects, which could explain the differences in predisposition to morphine abuse between one individual and another. These findings have important implications for the use of these rat strains in translational morphine and opiate research.

show abstract

Modelling Differential Vulnerability to Substance Use Disorder in Rodents: Neurobiological Mechanisms

Cited by 6 publications

References 228 publications

Cocaine-seeking behaviour is differentially expressed in male and female mice exposed to maternal separation and is associated with alterations in AMPA receptors subunits in the medial prefrontal cortex.

Cocaine-seeking behaviour is differentially expressed in male and female mice exposed to maternal separation and is associated with alterations in AMPA receptors subunits in the medial prefrontal cortex.

Neuroimaging Reveals Distinct Brain Glucose Metabolism Patterns Associated with Morphine Consumption in Two Inbreed Rat Models

Neuroimaging reveals distinct brain glucose metabolism patterns associated with morphine consumption in Lewis and Fischer 344 rat strains

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