Neurobiology of addiction: reward, tolerance, dependence and withdrawal
Mesolimbic dopamine and the three-stage addiction cycle, the receptor mechanisms by which each drug class raises dopamine, cellular tolerance and sensitisation, allostasis and the anti-reward systems that drive withdrawal, and how these explain agonist treatment and relapse.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Every drug with addictive potential raises dopamine in the nucleus accumbens, but each class reaches that end point by a different receptor mechanism. Exams test the mechanism, not the common pathway.
- Addiction runs as a three-stage cycle: binge/intoxication, withdrawal/negative affect, preoccupation/anticipation. Each stage maps to a circuit and to a treatment target.
- Tolerance, dependence and addiction are separate. Tolerance and physical dependence are normal adaptations and occur with therapeutic opioids or benzodiazepines; addiction adds compulsive use despite harm.
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Sources
- Neurobiology of addiction: a neurocircuitry analysisLancet Psychiatry (Koob and Volkow, 2016;3:760-73), 2016
- Neurobiologic advances from the brain disease model of addictionNew England Journal of Medicine (Volkow, Koob and McLellan, 2016;374:363-71), 2016
- Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th ed.)McGraw Hill (Brunton and Knollmann, 2023), 2023
- Rang & Dale's Pharmacology (10th ed.)Elsevier (Ritter et al., 2023), 2023
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Last updated
- 14 November 2026
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