MOLECULAR BASIS OF RELAPSE IN DRUG ADDICTION
Addiction follows a chronic course, with periods of abstinence followed by relapse. Vulnerability to relapse can persist even after years of abstinence, suggesting that long-lasting and perhaps permanent neurobiological changes underlie addiction.
Long-term drug exposure produces many physiological e behavioural changes including tolerance, sensitization and dependence.
Dependence is an adapted physiological state of cells or systems that develops to compensate for excessive stimulation by a drug. When drug intake stops, unmasking of this adapted state leads to a withdrawal syndrome that may have physical components as well as affective and emotional components.
Relapse is one of the major problems in drug addiction treatment, but the molecular changes that occur in brain systems involved in habit formation and that might cause craving and relapse itself, are unclear. However, a new study conducted by Bamford and his colleagues from University of Seattle reveals that withdrawal from chronic methamphetamine exposure induces long-lasting changes in cholinergic receptors (AChRs) e dopaminergic D1 receptors (D1Rs) at corticostriatal synapses and altered synaptic functioning that is restored by the re-administration of the drug (Bamford N. S., et al. Repeated exposure to methamphetamine causes long-lasting presynaptic corticostriatal depression that is renormalized with drug readministration. Neuron 58, 89-103, 2008).
Dorsal striatum is an area that is thought to be involved in habit formation, and corticostriatal glutamate signalling seems to be crucial for behaviour related to drug seeking. The authors investigated corticostriatal synapses in mice using electrochemistry, electrophysiology and an optical imaging technique in which a fluorescent dye was used to quantify the release of glutamate in individual terminals in slice preparations.
Repeated administration of methamphetamine followed by a period of withdrawal resulted in a chronic presynaptic depression (CPD) lasting at least 140 days.
Experiments showed that dopamine is required to initiate this long-lasting synaptic changes but is not necessary for their maintenance, which is consequence of decreased chronic stimulation of corticostriatal release through nAChRs (nicotinic AChRs) and increased tonic inhibition through sensitized mAChRs (muscarinic AChRs).