The role of acetylcholine in drug addiction

Abstract

Acetylcholine ACh, is involved in many CNS functions like sensory and motor processing, sleep, nociception, memory, mood, stress response, attention, arousal, motivation and reward. Due to the interaction with the dopaminergic reward system mainly in the ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC), it is believed that ACh plays a significant role on the initiation and maintenance of the drug addiction. Substances affecting the cholinergic system by increasing the levels of ACh, like cholinesterase and butyrylcholinesterase inhibitors (donepezil, rivastigmine, physostigmine, tacrine, galantamine), reduced the symptoms of addiction in a drug-induced CPP test as well as locomotor activity caused by morphine, cocaine and heroin. Unfortunately, donepezil failed to inhibit methamphetamine-CPP as well as the locomotor sensitization caused by this drug. For comparison, it has been indicated that mice lacking M5 receptor showed a reduction in cocaine self-administration and morphine-induced CPP. The stimulation of M4 receptor decreased DA release in NAc and the administration of non-selective antagonist of mAChRs, scopolamine decreased cocaine-induced locomotor activity in rats. Moreover, mecamylamine, a noncompetitve antagonist of nAChRs, prevented the increase in cocaine consumption as well as blocked cocaine and amphetamine-induced behavioral sensitization. Thus, drugs affecting cholinergic transduction could be approached as potential therapeutic agents for patients who abuse different psychoactive substances. These issues, however, require further studies.