Polymorphism of Serotonin 5-HT Receptors as the Basis of the Multifunctionality of Serotonin

This review addresses a question at the junction of neurophysiology and neurogenetics – the multiplicity of types and subtypes of serotonin (5-HT) receptors and their roles in the physiological effects of the brain neurotransmitter serotonin. Particular attention is paid to comparison of the behavioral effects of related subtypes of 5-HT receptors – 5-HT₁ (5-HT_1A and 5-HT_1B) and 5-HT₂ (5-HT_2A and 5-HT_2C) receptors – which are involved in the mechanisms regulating behavior and psychopathology. Published data are presented, along with results obtained at the Laboratory for Behavioral Neurogenics, providing evidence that different types of 5-HT receptors can act in different directions as well as similarly, supplementing each other, in the control of physiological functions and behavior. The roles of 5-HT_1A and 5-HT_1B receptors in regulating aggressive behavior, sexual arousal, drinking behavior, and food consumption are discussed. Experimental results demonstrating reciprocal relationships between 5-HT_2A and 5-HT_2C receptors and interactions between 5-HT_1A and 5-HT₃ receptors are presented. These data provide evidence of a complex system for these interactions not only at the receptor level, but also with the involvement of genes controlling the main elements of the serotonin system. Interaction of receptors evidently underlies neuroplasticity and plays a significant role in compensatory processes and in adaptive mechanisms.