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"Brain dopamine response in human opioid addiction"
- Gail Critchlow, Tina Malhotra (8 September 2008)
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Gail Critchlow, Psychiatrist Addiction Psychiatry, Tina Malhotra
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gail.critchlow{at}obmh.nhs.uk Gail Critchlow, et al.
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Dr Gail Critchlow Consultant in Addiction Psychiatry Specialist Community Addictions Service (SCAS) Rectory Road Oxford OX4 1BU UK Dr Tina Malhotra Specialist Registrar in Addiction Psychiatry Specialist Community Addiction service (SCAS) Rectory Road Oxford OX4 1BU UK 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 additive behavior.2,3 The authors rightly note however that drug expectancy and incentive salience4 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 levels and 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 of a clinical syndrome. BMJ 1976; 1: 1058-61. |
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