A new strategy that normalizes neurotransmitter deficits common in withdrawal from long-term cocaine use may reduce cocaine-seeking behaviors. The research, led by Dr Richard Rothman of NIH, was published in Trends in Pharmacological Sciences.
Biogenic amine transporters are principal sites of action for cocaine. Since withdrawal from cocaine has been shown to produce a dual deficit of dopamine and serotonin, the researchers reviewed preclinical and clinical data that suggest that the development of compounds that release these neurotransmitters may be a strategy for the treatment of cocaine addiction.
Although previous studies have found that dopamine- and serotonin-releasing agents together or alone reduce drug-seeking behavior in animals, a major limitation of the dopamine-releasing agents is their stimulant and reinforcing properties. The studies that were reviewed show that the combination of dopamine and serotonin may reduce this abuse potential. The compound PAL287, which releases both dopamine and serotonin, was found to reduce cocaine self-administration in animals without being reinforcing.
Dysfunctional Anterior Prefrontal Cortex Found in Drug Abusers
The results of a study led by Dr Elin Lehrmann of the National Institute on Drug Abuse were reported in the online publication, in PLoS ONE. Autopsy findings showed changes in the anterior prefrontal cortex of persons who abused drugs. The brains showed a number of common gene changes that are consistent with diminished brain plasticity.
The histories and toxicology reports of 42 deceased drug abusers were compiled to determine the primary drug of abuse (cocaine, marijuana, or phencyclidine [PCP]). The level of expression of more than 9000 genes in tissue samples from the anterior prefrontal cortex was measured.
It was found that nearly 80% of the cases exhibited similar changes in genetic output, compared with controls. The alteration that takes place in the brain from these drugs can interfere with the drug abuser's long-term ability to make decisions.