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Brain dopamine response in human opioid addiction

  • Mark R.C. Daglish (a1), Tim M. Williams (a2), Sue J. Wilson (a3), Lindsay G. Taylor (a1), Chin B. Eap (a4), Marc Augsburger (a5), Christian Giroud (a5), David J. Brooks (a6), Judy S. Myles (a7), Paul Grasby (a6), Anne R. Lingford-Hughes (a1) and David J. Nutt (a3)...
Abstract
Background

Drugs of dependence cause dopamine release in the rat striatum. Human neuroimaging studies have shown an increase in dopamine in the equivalent region in response to stimulants and other drugs

Aims

We tested whether opioids provoke dopamine release and its relationship to the subjective experience

Method

In two combined studies 14 heroin addicts on methadone maintenance treatment underwent two positron emission tomography brain scans of the dopamine system using [11C]-raclopride following an injection of placebo and either 50 mg intravenous diamorphine or 10 mg subcutaneous hydromorphone in a double-blind, random order design

Results

Both opioids produced marked subjective and physiological effects, but no measurable change in [11C]-raclopride binding

Conclusions

The absence of a dopamine response to opioid agonists contrasts with that found with stimulant drugs and suggests dopamine may not play the same role in addiction to opioids. This questions the role of dopamine in the subjective experience of heroin in opioid addicts

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Copyright
Corresponding author
Professor David J. Nutt, Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. Email: david.j.nutt@bristol.ac.uk
Footnotes
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Declaration of interest

None.

Funding detailed in Acknowledgements.

Footnotes
References
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Brain dopamine response in human opioid addiction

  • Mark R.C. Daglish (a1), Tim M. Williams (a2), Sue J. Wilson (a3), Lindsay G. Taylor (a1), Chin B. Eap (a4), Marc Augsburger (a5), Christian Giroud (a5), David J. Brooks (a6), Judy S. Myles (a7), Paul Grasby (a6), Anne R. Lingford-Hughes (a1) and David J. Nutt (a3)...
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eLetters

"Brain dopamine response in human opioid addiction"

Gail Critchlow, Psychiatrist
08 September 2008

Dr Gail CritchlowConsultant in Addiction PsychiatrySpecialist Community Addictions Service (SCAS) Rectory Road OxfordOX4 1BUUK

Dr Tina MalhotraSpecialist Registrar in Addiction Psychiatry Specialist Community Addiction service (SCAS) Rectory Road OxfordOX4 1BUUK

Correspondence to Dr Critchlow, address as above.

Daglish et al1 examined one of the central issues in Addiction. We know that responses to addictive stimuli are unified by the idea that there is phasic dopamine firing in the shell of the nucleus accumbens and further abnormalities of the orbitofrontal cortex which drive additivebehavior.2,3

The authors rightly note however that drug expectancy and incentivesalience4 are more associated with dopamine release than the acute response to single drugs. The relevance of biological mechanisms of addition is related to drug seeking behavior, sometimes even in the absence of drugs themselves and not single drug effects. It is perhaps no surprise that stimulants cause a contingent dopamine high after drug administration which can be interfered with by tyrosine depletion5, as is their pharmacology, but these investigators could not find one with opioids.

The patients involved with the study were on varying levels of methadone treatment. Their mean methadone plasma levels were low compared with usual maintenance groups,6 reflecting possibly low prescribed levelsand a substantial time interval since consumption of the previous dose. Being an opioid agonist itself methadone clearly treats opiate withdrawal but in usual treatment doses alters addictive behavior as well, such as drug hunger, frequency, injecting and criminal activity.7 This is therefore likely to be an important confounder in potentially attenuating a purported dopamine-addictive behavior association. It is understandable that continued opioid use was possibly required by ethical considerations to allow further exposure to opioids in the study. The subjects were in mild withdrawal and some had had confirmed exposure to stimulants- and even possibly recent enough exposure to stimulants be biologically relevant without testing positive. We know that stimulants can decrease dopamine response after coming off them for a prolonged period and this may explain the anhedonia associated with abstinence.8

Recruiting subjects for study of the underlying mechanisms of addition is by no means easy. It would be interesting to see a study of drug expectancy in drug dependent patients who are not prescribed substitution therapy and are currently confirmed abstinent but not in withdrawal nor post stimulant withdrawal anhedonia. This would require at least 3 months abstinence but would still be relevant as it is accepted that dependence is an extremely long term process with reinstatement as a key part of diagnosis.9 This, however, in these days of mass methadone treatment this is getting harder and harder to find. Perhaps the most accessible study group would be in residential rehabilitation, again giving rise to an ethical question- should we purposely expose vulnerable addicts to drug related cues?

References

1. Daglish M, Williams T, Wilson S, et al. Brain dopamine response in human opioid addciton. B J Psych 2008; 193: 65-72.

2. Di Chiara G, Bassareo V, Fenu S, DeLuca M, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D. Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacogy 2004; 47 (1): 227-41.

3. Volkow N, Fowler J, Addciton, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerbral Cortex 2000; 10: 318-25.

4. Robinson T, Berridge K. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 1993; 18: 247- 91.

5. McTavish S, McPherson M, Sharp, T, Cowen P, Attenuation of some subjective effects of amphetamine following tyrosine depletion. J Psychopharmacol 1999; 13: 144-147.

6. Wolff K, Hay AWM. Plasma methadone monitoring with methadone maintenance treatment. Drug Alcohol Dependence 1994; 36: 69–71.

7. Farrell M, Ward J, Mattick R, Hall W, Stimson GV, de Jarlais D, Gossop M, Strang J. Methadone maintenance treatment in opiate dependence: a review. BMJ 1994; 309: 997–1001.

8. Volkow N, Wang G, Fowler J, Logan J, Gatle S, Hitzemann R, Chen A,Dewey S, Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 1997; 386: 830-3.

9. Edwards G, Gross M. Alcohol dependence, provisional description ofa clinical syndrome. BMJ 1976; 1: 1058-61.
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