Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system

Singh, Archana; Xie, Yang; Davis, Ashton; Wang, Zi-Jun

doi:10.1007/s00213-021-06024-1

Cited by 7 publications

(2 citation statements)

References 89 publications

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“…Oral self-administration was conducted in operant chambers (Med Associates, Fairfax, VT, USA) equipped with 2 nose-poke holes (1 active, 1 inactive) mounted with 2 stimulus lights in the same panel, a house light, and a metal rod floor ( Gancarz et al, 2015 ; Singh et al, 2022 ). According to publications ( Wade et al, 2008 ; Monroe and Radke, 2021 ), mice were subjected to daily 2-hour oral self-administration training, during which time each active nose-poke response resulted in the delivery of 27 μL water or fentanyl solution (10 μg/mL, a concentration inducing reliable operant responding that is distinguishable from non-drug cues under a fixed ratio 1 schedule; Wade et al, 2008 ) or sucrose solution (10%) on an fixed ratio 1 schedule.…”

Section: Methodsmentioning

confidence: 99%

IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice

Yue

Wang

et al. 2023

International Journal of Neuropsychopharmacology

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Background Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder with an enormous socioeconomic burden. Opioid overdose deaths have reached an epidemic level, especially for fentanyl. One of the biggest challenges to treat OUD is the relapse to drug seeking after prolonged abstinence. Abnormalities in insulin-like growth factor-1 (IGF-1) have been reported in various neurological and psychiatric disorders, including OUD. However, whether IGF-1 and its downstream signaling pathways are associated with relapse to fentanyl seeking remains unclear. Methods Mice were subjected to daily 2-h fentanyl (10 μg/ml, 27μl/infusion) oral self-administration training for 14 days, followed by 14-day fentanyl cessation. Expression levels of IGF-1/IGF-1 receptor (IGF-1R) and downstream signaling pathways in the dorsomedial prefrontal cortex (dmPFC) were detected. Then, IGF-1 was bilaterally microinjected into the dmPFC from fentanyl cessation day 9 to day 13. Fentanyl-seeking behavior and excitatory synaptic transmission of pyramidal neurons in PFC were evaluated. Results We found that 14-daycessation from fentanyl oral self-administration caused significant downregulation of IGF-1 and IGF-1R phosphorylation in the dmPFC. These changes were accompanied by inhibition of downstream Aktand S6 signaling pathway. In addition, local administration of IGF-1 in the dmPFC attenuated context-induced fentanyl-seeking behavior. Furthermore, electrophysiology and immunohistochemistry analyses showed that IGF-1 blocked fentanyl-induced reduction of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors-mediated excitatory synaptic transmission as well as synaptic expression of AMPAR and NMDAR subunits. Conclusions These results suggest that IGF-1 in the PFC plays a pivotal role in regulating fentanyl seeking after prolonged cessation from fentanyl oral self-administration.

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Section: Methodsmentioning

confidence: 99%

IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice

Yue

Wang

et al. 2023

International Journal of Neuropsychopharmacology

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“…Transcription factors (CREB, NF-κb) could exert a crucial role in dependence development by influencing the expression of numerous genes simultaneously [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Invited Expert Opinion- Bio-informatic and Limitation Di-rectives to Help Adopt Ge-netic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Re-quired Analytic Evidence to Induce Dopamine Homeo-statsis

Blum,

Gold,

Cadet

et al. 2023

MRAJ

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Addiction, albeit some disbelievers like Mark Lewis [1], is a chronic, relapsing brain disease, resulting in unwanted loss of control over both substance and non- substance behavioral addictions leading to serious adverse consequences [2]. Addiction scientists and clinicians face an incredible challenge in combatting the current opioid and alcohol use disorder (AUD) pandemic throughout the world. Provisional data from the Centers for Disease Control and Prevention (CDC) shows that from July 2021-2022, over 100,000 individuals living in the United States (US) died from a drug overdose, and 77,237 of those deaths were related to opioid use [3]. This number is expected to rise, and according to the US Surgeon General it is highly conceivable that by 2025 approximately 165,000 Americans will die from an opioid overdose. Alcohol abuse, according to data from the World Health Organization (WHO), results in 3 million deaths worldwide every year, which represents 5.3% of all deaths globally [4].

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Stress and addiction

Yates¹

2023

Determinants of Addiction

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Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system

Cited by 7 publications

References 89 publications

IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice

IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice

Invited Expert Opinion- Bio-informatic and Limitation Di-rectives to Help Adopt Ge-netic Addiction Risk Screening and Identify Preaddictive Reward Dysregulation: Re-quired Analytic Evidence to Induce Dopamine Homeo-statsis

Stress and addiction

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