[Neurobiological mechanisms of dependence: implication of serotonin]

Numerous data in both animals and humans have shown that the serotoninergic system in brain plays a key role in self-control behaviour, as a low serotoninergic tone is well known to be frequently associated with impulsivity, auto- and hetero-aggressive behaviour. Interestingly, repeated administration of addictive drugs such as cocaine actually induces a decrease in the brain serotoninergic tone, thereby promoting the loss of self-control which characterizes drug craving in dependent subjects. Indeed, extensive neurobiological studies showed that changes in central serotoninergic neurotransmission caused by chronic treatment with cocaine and other addictive drugs are in fact opposite to those produced by drugs which enhance serotoninergic neurotransmission such as selective serotonin reuptake inhibitors. Accordingly, the latter effect very probably accounts for the capacity of these antidepressants to promote autoinhibition, and reduce both craving and consumption of drugs. On this basis, it can be proposed that the combination of selected serotonin receptor ligands with substances having the capacity to reduce the reinforcing appetitive properties of drugs of abuse (such as cannabinoid receptor antagonists) might be a novel therapeutic approach of withdrawal in addicted subjects.