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Naltrexone modulate...
Naltrexone modulates dopamine release following chronic, but not acute amphetamine administration: a translational study
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- Jayaram-Lindstrom, N. (author)
- Karolinska Institutet,Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Guterstam, J. (author)
- Karolinska Institutet,Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Haggkvist, J. (author)
- Karolinska Institutet,Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Ericson, Mia, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden.
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- Malmlof, T. (author)
- Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Schilström, Björn (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Karolinska Inst, Sect Neuropsychopharmacol, Dept Physiol & Pharmacol, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden.
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- Halldin, C. (author)
- Karolinska Institutet,Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Cervenka, Simon (author)
- Karolinska Institutet,Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Saijo, T. (author)
- Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Nordstrom, A. L. (author)
- Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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- Franck, J. (author)
- Karolinska Institutet,Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden.
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Karolinska Institutet Stockholm Cty Council, Dept Clin Neurosci, Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden;Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden. (creator_code:org_t)
- 2017-04-25
- 2017
- English.
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7
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Abstract
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- The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [C-11]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to study the modulatory effects of naltrexone on dopamine levels after acute and chronic amphetamine exposure. In healthy humans, naltrexone attenuated the subjective effects of amphetamine, confirming our previous results. Amphetamine produced a significant reduction in striatal radioligand binding, indicating increased levels of endogenous dopamine. However, there was no statistically significant effect of naltrexone on dopamine release. The same pattern was observed in rats, where an acute injection of amphetamine caused a significant rise in striatal dopamine levels, with no effect of naltrexone pretreatment. However, in a chronic model, naltrexone significantly attenuated the dopamine release caused by reinstatement of amphetamine. Collectively, these data suggest that the opioid system becomes engaged during the more chronic phase of drug use, evidenced by the modulatory effect of naltrexone on dopamine release following chronic amphetamine administration. The importance of opioid-dopamine interactions in the reinforcing and addictive effects of amphetamine is highlighted by the present findings and may help to facilitate medication development in the field of stimulant dependence.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- POSITRON-EMISSION-TOMOGRAPHY
- MU-OPIOID RECEPTORS
- ORAL D-AMPHETAMINE
- HUMAN BRAIN
- NUCLEUS-ACCUMBENS
- EXTRACELLULAR DOPAMINE
- ANTAGONIST
- NALTREXONE
- SUBJECTIVE RESPONSE
- HEALTHY-VOLUNTEERS
- INDUCED INCREASES
Publication and Content Type
- ref (subject category)
- art (subject category)
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Jayaram-Lindstro ...
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Guterstam, J.
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Haggkvist, J.
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Ericson, Mia, 19 ...
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Malmlof, T.
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Schilström, Björ ...
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Halldin, C.
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Cervenka, Simon
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Saijo, T.
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Nordstrom, A. L.
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Franck, J.
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- MEDICAL AND HEALTH SCIENCES
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University of Gothenburg
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Karolinska Institutet
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Uppsala University