Relapse to drug and alcohol use: a matter of sensitization

2000 ◽  
Vol 12 (1) ◽  
pp. 5-8 ◽  
Author(s):  
A.N.M. Schoffelmeer ◽  
L.J.M.J. Vanderschuren ◽  
A.H. Mulder ◽  
E.H. Jacobs ◽  
T.J. De Vries
Keyword(s):  
Behavioral Sensitization ◽  
Alcohol Addiction ◽  
Behavioral Effects ◽  
Self Administration ◽  
Behavioral Studies ◽  
Seeking Behavior ◽  
Drug And Alcohol Use ◽  
Biochemical Research ◽  
Drug And Alcohol ◽  
The Brain

SUMMARYRepeated exposure of rats to cocaine, amphetamine, opiates, nicotine and alcohol causes a very long-lasting (months) increase in the behavioral effects of these addictive drugs and drug-associated environmental stimuli (sensitization). This hypersensitivity is associated with persistent changes in the reactivity of neurons of the motivational (mesocorticolim-bic) system in the brain. Using an animal model for relapse, recent studies in our laboratory show that relapse to drug-seeking behavior (following extinction of intravenous cocaine or heroin self-administration) depends on the occurrence of sensitization. Accordingly, sensitization and conditioning seem to be more important for the persistence of drug and alcohol addiction then the occurrence of withdrawal phenomena. Biochemical research on the molecular and cellular basis of behavioral sensitization and behavioral studies on readjustment of stimulus responsiveness in rats, is of great importance for the development of an adequate pharmacotherapy of addiction.

scholarly journals Does Prenatal Methamphetamine Exposure Induce Sensitization to Drugs in Adulthood?

2017 ◽  
pp. S457-S467 ◽  
Author(s):  
E. MACÚCHOVÁ ◽  
R. ŠLAMBEROVÁ
Keyword(s):  
Infant Development ◽  
Drug Exposure ◽  
Behavioral Sensitization ◽  
Drug Effects ◽  
Mechanisms Of Action ◽  
Prenatal Drug Exposure ◽  
Self Administration ◽  
Psychomotor Activity ◽  
Seeking Behavior ◽  
Reward Pathways

Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing behavioral cross-sensitization, after prenatal methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drug-seeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.

Prevention of drug and alcohol addiction

Globus ◽  
2019 ◽  
Vol 34 (6) ◽  
Author(s):  
P.P. Bartaeva ◽  
D.A. Zhigzhitov ◽  
V.E. Coj ◽  
A.V. Tokarev
Keyword(s):  
Alcohol Addiction ◽  
Drug And Alcohol

scholarly journals The Adenosine A2A Receptor Activation in Nucleus Accumbens Suppress Cue-Induced Reinstatement of Propofol Self-administration in Rats

2021 ◽  
Author(s):  
Zhanglei Dong ◽  
Bingwu Huang ◽  
Chenchen Jiang ◽  
Jiangfan Chen ◽  
Han Lin ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
D2 Receptor ◽  
Fixed Ratio ◽  
Receptor Activation ◽  
Addictive Behaviors ◽  
Self Administration ◽  
A2a Receptors ◽  
Mediated Effects ◽  
Seeking Behavior ◽  
Adenosine A2a

AbstractPropofol has shown strong addictive properties in rats and humans. Adenosine A2A receptors (A2AR) in the nucleus accumbens (NAc) modulate dopamine signal and addictive behaviors such as cocaine- and amphetamine-induced self-administration. However, whether A2AR can modulate propofol addiction remains unknown. AAV-shA2AR was intra-NAc injected 3 weeks before the propofol self-administration training to test the impacts of NAc A2AR on establishing the self-administration model with fixed ratio 1 (FR1) schedule. Thereafter, the rats were withdrawal from propofol for 14 days and tested cue-induced reinstatement of propofol seeking behavior on day 15. The propofol withdrawal rats received one of the doses of CGS21680 (A2AR agonist, 2.5–10.0 ng/site), MSX-3 (A2AR antagonist, 5.0–20.0 μg/site) or eticlopride (D2 receptor (D2R) antagonist, 0.75–3.0 μg/site) or vehicle via intra-NAc injection before relapse behavior test. The numbers of active and inactive nose-poke response were recorded. Focal knockdown A2AR by shA2AR did not affect the acquisition of propofol self-administration behavior, but enhance cue-induced reinstatement of propofol self-administration compared with the AAV-shCTRLgroup. Pharmacological activation of the A2AR by CGS21680 (≥ 5.0 ng/site) attenuated cue-induced reinstatement of propofol self-administration behavior. Similarly, pharmacological blockade of D2R by eticlopride (0.75–3.0 μg/site) attenuated propofol seeking behavior. These effects were reversed by the administration of MSX-3 (5.0–20.0 μg/site). The A2AR- and D2R-mediated effects on propofol relapse were not confounded by the learning process, and motor activity as the sucrose self-administration and locomotor activity were not affected by all the treatments. This study provides genetic and pharmacological evidence that NAc A2AR activation suppresses cue-induced propofol relapse in rats, possibly by interacting with D2R.

scholarly journals The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization

2021 ◽  
Author(s):  
Marlaina R. Stocco ◽  
Ahmed A. El-Sherbeni ◽  
Bin Zhao ◽  
Maria Novalen ◽  
Rachel F. Tyndale
Keyword(s):  
Neurotransmitter Release ◽  
Behavioral Sensitization ◽  
Serotonin Release ◽  
Striatal Dopamine ◽  
Irreversible Inhibitor ◽  
Drug Concentrations ◽  
Metabolite Concentrations ◽  
The Brain

Abstract Rationale Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats. Methods To investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release. Results CYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization. Conclusions CYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

The use of chatbots as supportive agents for people seeking help for drug and alcohol addiction: A systematic review. (Preprint)

2021 ◽  
Author(s):  
Lisa Ogilvie ◽  
Jerome Carson ◽  
Julie Prescott
Keyword(s):  
Mixed Methods ◽  
Healthcare Setting ◽  
The Body ◽  
Alcohol Addiction ◽  
Bibliographic Databases ◽  
Ethical Implications ◽  
Qualitative Work ◽  
Meta Analyses ◽  
Future Work ◽  
Drug And Alcohol

BACKGROUND The use of chatbots in healthcare is an area of study receiving increased academic interest. As the knowledge base grows, the granularity in the level of research is being refined, seeing more targeted work in specific areas of healthcare, for example, chatbots for anxiety and depression, cancer care, and pregnancy support. This paper focuses on the targeted application of chatbots in drug and alcohol addiction. OBJECTIVE The aim of this paper is to systematically review and summarise the research conducted on the use of chatbots in the field of addiction, specifically the use of chatbots as supportive agents for those who suffer from drug and alcohol addiction. METHODS A systematic search of bibliographic databases using the broad search criteria of “chatbot and addiction,” identified papers for screening. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Mixed Methods Appraisal Tool were used, which resulted in the quality assessment and review of 5 papers. RESULTS Although the body of research in this field is limited, what has been published shows promising results. A combination of quantitative, qualitative, and mixed methods studies were reviewed, among which statistically significant findings were reported on the efficacy of chatbots targeted at drug and alcohol addiction. These findings were also substantiated in the qualitative work reviewed. A strong message of caution was conveyed however on the ethical implications of using chatbots to afford support to addicted individuals. CONCLUSIONS The literature reviewed shows that more work is needed to appreciate solutions that leverage existing data, such as big data available from social media, or that which is accessed by prevalent market leading chatbots. It also highlighted ethical concerns over the use of a non-human agent to afford support to those with drug and alcohol addiction. It was reported however, that statistically significant results were returned for ‘bespoke’ chatbots in this area of healthcare, setting a promising foundation for future work.

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