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).