Chapter 15 - Critical Role of Cannabinoid CB1 Receptors in Nicotine Reward and Addiction

Abstract

The brain endocannabinoid system is involved in modulating motivation and reward processes. Endocannabinoids, as synaptic retrograde messengers, mediate neurotransmitter release by activating the presynaptic cannabinoid type 1 (CB1) receptors at both excitatory and inhibitory synapses. In this chapter, we present an overview of some important concepts related to the involvement of the endocannabinoid system in nicotine reward processing through CB1 receptor signaling. Nicotine use and dependence directly affect neural reward pathways, enhancing dopamine release. Preclinical and clinical studies have indicated that there is a functional interaction between cholinergic nicotinic and endocannabinoid systems in synaptic plasticity and drug addiction. Pharmacological activation, blockage, or genetic deletion of CB1 receptors in the mesocorticolimbic reward system influences the abuse-related behavioral effects of nicotine. On the other hand, chronic nicotine administration causes a change in the expression of CB1 receptors and also in the endocannabinoid levels of the brain, suggesting a role for the endocannabinoid system in the nicotine reward process, especially, via CB1 receptors.