scholarly journals Context-induced relapse to drug seeking: a review

2008 ◽  
Vol 363 (1507) ◽  
pp. 3233-3243 ◽  
Author(s):  
Hans S Crombag ◽  
Jennifer M Bossert ◽  
Eisuke Koya ◽  
Yavin Shaham
Keyword(s):  
Basolateral Amygdala ◽  
Dorsal Hippocampus ◽  
Dorsal Striatum ◽  
Self Administration ◽  
Occasion Setting ◽  
Drug Seeking ◽  
Psychological Mechanisms ◽  
History Of ◽  
Study Context

In humans, exposure to environmental contexts previously associated with drug intake often provokes relapse to drug use, but the mechanisms mediating this relapse are unknown. Based on early studies by Bouton & Bolles on context-induced ‘renewal’ of learned behaviours, we developed a procedure to study context-induced relapse to drug seeking. In this procedure, rats are first trained to self-administer drug in one context. Next, drug-reinforced lever responding is extinguished in a different (non-drug) context. Subsequently, context-induced reinstatement of drug seeking is assessed by re-exposing rats to the drug-associated context. Using variations of this procedure, we and others reported reliable context-induced reinstatement in rats with a history of heroin, cocaine, heroin–cocaine combination, alcohol and nicotine self-administration. Here, we first discuss potential psychological mechanisms of context-induced reinstatement, including excitatory and inhibitory Pavlovian conditioning, and occasion setting. We then summarize results from pharmacological and neuroanatomical studies on the role of several neurotransmitter systems (dopamine, glutamate, serotonin and opioids) and brain areas (ventral tegmental area, accumbens shell, dorsal striatum, basolateral amygdala, prefrontal cortex, dorsal hippocampus and lateral hypothalamus) in context-induced reinstatement. We conclude by discussing the clinical implications of rat studies on context-induced reinstatement of drug seeking.

Central, but not basolateral, amygdala involvement in the anxiolytic-like effects of midazolam in rats in the elevated plus maze

2010 ◽  
Vol 26 (4) ◽  
pp. 543-554 ◽  
Author(s):  
Milene C Carvalho ◽  
Caio M Moreira ◽  
Janaína M Zanoveli ◽  
Marcus L Brandão
Keyword(s):  
Basolateral Amygdala ◽  
Elevated Plus Maze ◽  
Dorsal Hippocampus ◽  
Dorsal Striatum ◽  
Input And Output ◽  
Plus Maze ◽  
Main Input ◽  
Fear And Anxiety ◽  
Behavior Of Rats

The role of the amygdala in the mediation of fear and anxiety has been extensively investigated. However, how the amygdala functions during the organization of the anxiety-like behaviors generated in the elevated plus maze (EPM) is still under investigation. The basolateral (BLA) and the central (CeA) nuclei are the main input and output stations of the amygdala. In the present study, we ethopharmacologically analyzed the behavior of rats subjected to the EPM and the tissue content of the monoamines dopamine (DA) and serotonin (5-HT) and their metabolites in the nucleus accumbens (NAc), dorsal hippocampus (DH), and dorsal striatum (DS) of animals injected with saline or midazolam (20 and 30 nmol/0.2 µL) into the BLA or CeA. Injections of midazolam into the CeA, but not BLA, caused clear anxiolytic-like effects in the EPM. These treatments did not cause significant changes in 5-HT or DA contents in the NAc, DH, or DS of animals tested in the EPM. The data suggest that the anxiolytic-like effects of midazolam in the EPM also appear to rely on GABA-benzodiazepine mechanisms in the CeA, but not BLA, and do not appear to depend on 5-HT and DA mechanisms prevalent in limbic structures.

The Future of Addiction and Recovery Healing Arts

2018 ◽  
Author(s):  
Shahla J. Modir ◽  
George E. Muñoz
Keyword(s):  
Addiction Treatment ◽  
Basolateral Amygdala ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Outcome Data ◽  
Neural Imaging ◽  
Transcranial Magnetic Brain Stimulation ◽  
The Future ◽  
Healing Arts

This chapter peers into the future of addiction treatment. It begins with an exploration of repetitive transcranial magnetic brain stimulation or rTMS as a treatment for SUD. The evidence and clinical data is reviewed. Findings include outcome data on the use of rTMS. Furthermore, important brain regions central to the development of SUD are examined: the ventral tegmental area and ventral striatum appear to play a central role in the binge/intoxication stage, the extended amygdala in the withdrawal/negative affect stage, and the orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula in craving. The role of genomics and gene-wide associations to deliver future personalized addiction treatments is discussed as is advanced functional neural imaging. Technology for patients and consumers, including relapse prevention apps and bidirectional biometric reading is mentioned. Breakthroughs in addiction immunology, both generalized and substance specific, are discussed as potential points of future study and interventions.

Yu.F. Samarin and Discussions on the All-class Zemstvo in the Works of Russian Conservatives in Post-reform Russia

2019 ◽  
Vol 54 ◽  
pp. 93-101
Author(s):  
Maria A.  Saevskaya
Keyword(s):  
Dominant Role ◽  
Russian Empire ◽  
Self Administration ◽  
Political Events ◽  
History Of ◽  
The Russian Empire

Local self-administration was introduced in Russia by the Tsar Alexander II “Liberator” in 1864 and became one of the most important political events in the Russian Empire of that time. The new reform immediately sparked vigorous discussions on how exactly the Russian Zemstvo should be organized. The question of the role and importance of classes in Zemstvo institutions became most important. The Russian conservatives were also looking for the answer. Some of them considered that it was necessary to defend the old imperial order and the dominant role of the nobility, others hoped that Zemstvo would become a nationwide force based on the principle of the participation of all classes. Yu. F. Samarin, Zemstvo leader, Slavophil and the author of the most prominent project on the history of Zemstvo in Russia, supported the second alternative. He consistently criticized the idyll of the nobility domination in Zemstvo, asserted the ability of the peasants for self-government, and supported introducing the principle of all-classes representation in Zemstvo institutions of the Russian empire.

scholarly journals Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration

2018 ◽  
Vol 56 (5) ◽  
pp. 3603-3615 ◽  
Author(s):  
Christopher A. Blackwood ◽  
Reece Hoerle ◽  
Michael Leary ◽  
Jennifer Schroeder ◽  
Martin O. Job ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Self Administration ◽  
Drug Seeking

scholarly journals Blockade of β-Adrenergic Receptors by Propranolol Disrupts Reconsolidation of Drug Memory and Attenuates Heroin Seeking

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangpei Chen ◽  
Shihao Huang ◽  
Chang Yang ◽  
Feilong Wu ◽  
Qiuyao Zheng ◽  
...  
Keyword(s):  
Relapse Prevention ◽  
Adrenergic Receptors ◽  
Time Windows ◽  
Stimulus Exposure ◽  
Self Administration ◽  
Pharmacological Interventions ◽  
Drug Seeking ◽  
History Of ◽  
Propranolol Treatment ◽  
Β Adrenergic Receptors

Persistent traces of drug reward memories contribute to intense craving and often trigger relapse. A number of pharmacological interventions on drug-associated memories have shown significant benefits in relapse prevention at a preclinical level but their translational potential is limited due to deleterious side effects. Propranolol, a non-specific β-adrenergic receptors antagonist, is known for its ability to erase maladaptive memories associated with nicotine or cocaine in rodents and humans. However, little is known about its effect on reconsolidation of heroin memory and heroin seeking. In the present study, rats with a history of intravenous heroin self-administration received the propranolol treatment (10 mg/kg; i.p.) at different time windows with or without CS (conditioned stimulus) exposure. Our results showed that propranolol, when administered immediately after CS exposure but not 6 h later, can significantly attenuate cue-induced and drug-primed reinstatement of heroin seeking, suggesting that propranolol has the ability to disrupt heroin memory and reduce relapse. The propranolol treatment without retrieval of drug memory had no effect on subsequent reinstatement of heroin seeking, suggesting that its interfering effects are retrieval-dependent. Importantly, the effects of propranolol were long lasting as rats showed diminished drug seeking even 28 days after the treatment. Altogether, our study suggests that propranolol can interfere with reconsolidation of heroin memory and reduce subsequent drug seeking, making it an attractive therapeutic candidate for the treatment of opioid addiction and relapse prevention.

scholarly journals Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence

2021 ◽  
Author(s):  
Ida Fredriksson ◽  
Aniruddha Shekara ◽  
Sarah V. Applebey ◽  
Angelica Minier-Toribio ◽  
Lindsay Altidor ◽  
...  
Keyword(s):  
Rat Model ◽  
Female Rats ◽  
Sprague Dawley ◽  
Self Administration ◽  
Drug Seeking ◽  
Neuronal Ensembles ◽  
Ventral Subiculum ◽  
Activity Marker ◽  
Electric Barrier

AbstractWe recently developed a rat model of incubation of oxycodone craving where opioid seeking progressively increases after voluntary suppression of drug self-administration by adverse consequences of drug seeking. Here, we studied the role of ventral subiculum (vSub) neuronal ensembles in this incubation, using the activity marker Fos, muscimol-baclofen (GABAergic agonists) inactivation, and Daun02 chemogenetic inactivation.We trained Sprague-Dawley or Fos-lacZ transgenic male and female rats to self-administer oxycodone (0.1 mg/kg/infusion, 6-h/d) for 14 days. The rats were then exposed for 14 days to an electric barrier of increasing intensity (0.1 to 0.4 mA) near the drug-paired lever that caused voluntary abstinence or were exposed to 14 days of forced abstinence. We tested Sprague-Dawley rats for relapse to oxycodone seeking without shock and drug on abstinence day 15 and extracted their brains for Fos-immunohistochemistry, or tested them after vSub vehicle or muscimol-baclofen injections on abstinence days 1 and 15. We performed Daun02 inactivation of relapse-activated vSub Fos neurons in Fos-lacZ transgenic rats on abstinence day 15 and then tested them for relapse on abstinence day 18.Relapse after electric barrier-induced abstinence increased Fos expression in vSub. Muscimol-baclofen inactivation or Daun02 selective inactivation of vSub Fos-expressing neuronal ensembles decreased “incubated” oxycodone seeking after voluntary abstinence. Muscimol-baclofen vSub inactivation had no effect on non-incubated opioid seeking on abstinence day 1 or incubation after forced abstinence.Our results demonstrate a selective role of vSub neuronal ensembles in incubation of opioid craving after cessation of drug self-administration by adverse consequences of drug seeking.Significance statementHigh relapse rate is a cardinal feature of opioid addiction and a major impediment for successful treatment. In humans, abstinence is often self-imposed, and relapse typically involves a conflict situation between the desire to experience the drug’s rewarding effects and negative consequences of drug seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence. Here, we used the activity marker Fos, muscimol-baclofen (GABAergic agonists) inactivation, and Daun02 chemogenetic inactivation to demonstrate a selective role of vSub neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence, but not in incubation of opioid craving after forced abstinence or non-incubated opioid seeking during early abstinence.

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