The DOI matches its Crossref record; 456 of the 456 references it cites were found in a registry or an index.
Neurobiological Similarities in Depression and Drug Dependence: A Self-Medication Hypothesis
Abstract
Epidemiological and clinical data indicate high comorbidity between depression and drug dependence that may reflect an attempt to self-medicate with drugs of abuse. The present review examines whether these two psychiatric disorders are related by attempting to identify similarities in the neurobiology of depression and drug dependence. Emphasis is put on the neuromechanisms that may mediate specific core symptoms of both disorders that reflect alterations in reward and motivational processes. First, the epidemiological and clinical data on the comorbidity of the two disorders are reviewed briefly. Then, the neuroadaptations associated with psychomotor stimulant, opiate, ethanol, nicotine, and benzodiazepine dependence in animals are reviewed. Finally, the neurotransmitter systems whose function appears to be altered in depression (i.e., serotonin, norepinephrine, acetylcholine, dopamine, gamma-aminobutyric acid, corticotropin releasing factor, neuropeptide Y, and somatostatin), as revealed primarily by animal studies, are discussed. It is concluded that drug dependence and depression may be associated with alterations in some of the same neurotransmitter systems and, in particular, with alterations of neurotransmitter function in limbic-related brain structures. Thus, these two psychiatric disorders may be linked by some shared neurobiology. Nevertheless, it remains unclear whether drug abuse and depression are different symptomatic expressions of the same preexisting neurobiological abnormalities, or whether repeated drug abuse leads to the abnormalities mediating depression (i.e., drug-induced depressions). The hypothesis of self-medication of non-drug- and drug-induced depressions with drugs of abuse is also discussed as a potentially important explanatory concept in understanding the observed clinical comorbidity of these two psychiatric disorders.
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“it is believed that some depressed patients initiate smoking as an attempt to self medicate depressive symptoms with nicotine (Markou et al., 1998; Patton et al., 1998).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Markou et al., 1998
In the citing paper
“Depression and anxiety are both highly comorbid with nicotine dependence (Paperwalla et al., 2004), and nicotine use may be an attempt at self-medication in these conditions (Markou et al., 1998).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Markou et al., 1998
In the citing paper
“These findings suggest that chronic drug taking leading to hypo-activity of the meso-ventromedial striatal dopamine system may result in a negative mood state which in turn accelerates drug-taking (“self-medication”) in an attempt to improve the mood state (Markou et al., 1998).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Markou et al., 1998
In the citing paper
“According to the self-medication hypothesis of nicotine dependence (Carmody, 1992; Markou, Kosten, & Koob, 1998; Pomerleau & Pomerleau, 1985), this might be because nicotine reduces negative affect and works as an antidepressant.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Markou et al., 1998
Citations
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Cellular and molecular mechanisms of drug dependence
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Cited by
Sorted by citations
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340
Reconsidering anhedonia in depression: Lessons from translational neuroscience
Treadway, M. T., & Zald, D. H. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.06.006 · Cited by 1,579
Ikemoto, S. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.004 · Cited by 1,477
Addiction and the brain antireward system
Koob, G. F., & Le Moal, M. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093548 · Cited by 1,457
The association of cigarette smoking with depression and anxiety: a systematic review
Fluharty, M., Taylor, A. E., Grabski, M., & Munafò, M. R. (2017) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw140 · Cited by 1,299
Metadata
- Authors
- Markou, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Markou, A
- Venue
- Neuropsychopharmacology
- Published
- 1998-03
- Volume
- 18
- Issue
- 3
- Pages
- 135-174
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W2042152382
- Cited by
- 767
- References
- 456
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 24 · 2023: 21 · 2022: 17 · 2021: 30 · 2020: 22 · 2019: 15 · 2018: 26 · 2017: 21 · 2016: 26 · 2015: 37 · 2014: 28 · 2013: 28 · 2012: 26
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50da004060-13)
- National Institute on Drug Abuse (DA 00213, DA04060, DA 00112)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- depression, drug addiction, self-medication hypothesis, comorbidities, reward and motivation, neurotransmitter systems, limbic system, stimulant use disorder, opioid use disorder, ethanol dependence, nicotine dependence, benzodiazepine dependence, drug-induced depression, serotonin, norepinephrine, dopamine, GABA, neuropeptide Y, somatostatin, corticotropin-releasing factor
- MeSH terms
- Animals, Brain, Corticotropin-Releasing Hormone, Depressive Disorder, Neuropeptide Y, Norepinephrine, Serotonin, Comorbidity, Substance-Related Disorders
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