Nicotinic Acetylcholine Receptors, Cannabinoid Receptors, and Their Interplay in Drug Addiction

Identifying the changes that take place at the molecular, cellular, and neurocircuitry levels is of key importance to understanding the neurobiological mechanisms involved in drug addiction, currently considered a chronic neuropsychiatric disorder. Nicotinic acetylcholine receptors (nAChRs) are a Cys-loop gene family of neurotransmitter receptors belonging to the superfamily of pentameric ligand-gated cation channels. The neuronal-type nAChRs are expressed in mammalian brain, playing a critical role in various addictive disorders. The ample combinatorial diversity of nAChR subtypes explains the diversity of functional responses to different drugs and chemical compounds that these neurotransmitter receptors undergo in different brain regions. Cannabis is increasingly becoming one of the most widespread addictive drugs, and its receptors in brain show macro- and microanatomical overlap with some subtypes of nAChRs. Cannabinoid receptors are important homeostatic modulators of neuronal activity in the central nervous system, and their interaction with nAChRs is not only anatomical but functional. Neuroadaptations, including the down- or upregulation of selective nAChR subtypes, the modulation of neurotransmitter release and neuronal scaffolding proteins, and the consequent strengthening or weakening of synapses form part of the varied palette of mechanisms involving the ubiquitous nAChR molecule in response to drug addiction, some of which imply crosstalk with cannabinoid receptors.