Neural Substrates and Circuits of Drug Addiction

A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine’s reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect—reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.

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Substance use disorders and the mechanisms of drug addiction

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780198713005.003.0048 ◽

2020 ◽

pp. 477-491

Author(s):

Trevor W. Robbins ◽

Barry J. Everitt

Keyword(s):

Drug Addiction ◽

Positive Reinforcement ◽

Animal Studies ◽

Dorsal Striatum ◽

Critical Issue ◽

Neural Substrates ◽

Future Prospects ◽

Self Administration ◽

Limbic Systems ◽

Brain Changes

The understanding of drug addiction has gained much from a neuroscientific approach, reflected by changing approaches in diagnosis. The two main psychological accounts of addiction to substances, ranging from alcohol and nicotine to opioids and stimulant drugs, are opponent motivational processing, emphasizing the importance of withdrawal symptoms, and aberrant learning from positive reinforcement. The neural and neurochemical systems implicated have been identified on the basis of animal studies, using especially the self-administration paradigm, and human investigations employing a range of brain imaging modalities. These neural substrates include dopamine-dependent functions of the ventral and dorsal striatum, as well as regulatory influences of fronto-limbic systems. The chapter considers the critical issue of cause and effect, and whether brain changes reflect neurotoxic effects of abuse or whether there are predisposing neurobehavioural factors. It also outlines the current situation and future prospects for treatment by medication, possibly in association with psychological approaches.

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The susceptibility of compulsive traits and neural substrates of the prefrontal and anti-reward systems implicated in drug addiction

Advances in Psychological Science ◽

10.3724/sp.j.1042.2021.01345 ◽

2021 ◽

Vol 29 (8) ◽

pp. 1345

Author(s):

Wan-Sen YAN ◽

Su-Jiao LIU ◽

Ran-Ran ZHANG ◽

Peng XU

Keyword(s):

Drug Addiction ◽

Neural Substrates ◽

Reward Systems

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Neural substrates of drug craving and relapse in drug addiction

Annals of Medicine ◽

10.3109/07853899809029938 ◽

1998 ◽

Vol 30 (4) ◽

pp. 379-389 ◽

Cited By ~ 84

Author(s):

David W Self

Keyword(s):

Drug Addiction ◽

Neural Substrates ◽

Drug Craving

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Lessons From the Neural Bases of Speech and Voice

Perspectives on Speech Science and Orofacial Disorders ◽

10.1044/ssod21.1.5 ◽

2011 ◽

Vol 21 (1) ◽

pp. 5-14

Author(s):

Christy L. Ludlow

Keyword(s):

Brain Networks ◽

Neural Substrates ◽

Voice Behavior ◽

Therapeutic Approaches ◽

Neural Bases ◽

Sound Foundation ◽

The Brain ◽

Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

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The treatment of drug addiction

JAMA ◽

10.1001/jama.194.6.680a ◽

1965 ◽

Vol 194 (6) ◽

pp. 680a-681

Author(s):

V. H. Vogel

Keyword(s):

Drug Addiction

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Sinn und Unsinn von Systemen zum Monitoring von Suchtbehandlung – Nationale und internationale Erfahrungen

SUCHT - Zeitschrift für Wissenschaft und Praxis / Journal of Addiction Research and Practice ◽

10.1024/0939-5911/a000637 ◽

2020 ◽

Vol 66 (1) ◽

pp. 13-20 ◽

Cited By ~ 1

Author(s):

Roland Simon

Keyword(s):

United Nations ◽

Drug Addiction ◽

Monitoring Centre ◽

Sind Eine ◽

Drugs And Crime

Zusammenfassung. Zielsetzung: Monitoringsysteme für die Behandlung von Substanzbezogenen Störungen (MfS) werden eingesetzt, um den Gesundheitszustand der Zielgruppe, Interventionen und deren Ergebnisse zu erfassen. Die Entwicklung der bestehenden Systeme, Möglichkeiten und Probleme werden untersucht. Methodik: Da MfS selten Gegenstand wissenschaftlicher Publikationen sind, wurden, ausgehend von zentralen Publikationen des European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), der Pompidou-Gruppe und der Weltgesundheitsorganisation (WHO) / United Nations Office on Drugs and Crime (UNODC) relevante Publikationen gesucht. Diese sind, zusammen mit der langjährigen Erfahrung in deutschen und europäischen MfS, Grundlage der Darstellung. Ergebnisse: Ähnliche Bedingungen und ein regelmäßiger Austausch haben zu Gemeinsamkeiten bei nationalen und internationalen MfS geführt. Zentrale Merkmale sind: eine Vielzahl beteiligter Akteure aus Versorgung, Finanzierung, Wissenschaft, Technik und Administration; Themenfelder: Verfügbarkeit und Zugang, Effektivität und Effizienz, Akzeptanz und Nutzung von Behandlung; Erhebungseinheiten: Klient, Therapeut, Einrichtung, Behandlung und Ergebnisse. Daten aus der Routineerhebung werden in meist anonymisierter Form regelmäßig zusammengeführt und berichtet. Zentrale Ziele sind dabei die Erkennung von Trends und Veränderungen, Abschätzung von Bedarf und Rückmeldung über die Effekte von Interventionen. Als kritisch erwiesen sich die Repräsentativität der Stichproben, nicht zu kontrollierende Einflussfaktoren und Probleme der Vergleichbarkeit zwischen Regionen, Teilgruppen und über die Zeit. Schlussfolgerungen: MfS sollten trotz methodischer Probleme und Einschränkungen weiter verwendet werden, da Informationen zu Behandlungsbedarf, Durchführung und Ergebnissen von Interventionen im Bereich der Suchthilfe zeitnah notwendig sind und alternative Datenquellen fehlen. Eine klarere Zielsetzung und bessere Konzeption, langfristige Perspektiven, Unabhängigkeit und Qualitätssicherung, eine kritische Interpretation der Ergebnisse und eine bessere Verknüpfung zwischen MfS, anderen Datenquellen und wissenschaftlicher Forschung könnten Wert und Bedeutung von MfS deutlich erhöhen.

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