The 5-HT7 receptor as a potential target for treating drug and alcohol abuse.

Sheketha R Hauser,Richard L Bell,Peter B Hedlund,Eric A Engleman,Amanda J Roberts,Youssef Sari

doi:10.3389/fnins.2014.00448

Abstract

Alcohol and drug abuse take a large toll on society and affected individuals. However, very few effective treatments are currently available to treat alcohol and drug addiction. Basic and clinical research has begun to provide some insights into the underlying neurobiological systems involved in the addiction process. Several neurotransmitter pathways have been implicated and distinct reward neurocircuitry have been proposed—including the mesocorticolimbic dopamine (MCL-DA) system and the extended amygdala. The serotonin (5-HT) neurotransmitter system is of particular interest and multiple 5-HT receptors are thought to play significant roles in alcohol and drug self-administration and the development of drug dependence. Among the 5-HT receptors, the 5-HT7 receptor is currently undergoing characterization as a potential target for the treatment of several psychiatric disorders. Although this receptor has received only limited research regarding addictive behaviors, aspects of its neuroanatomical, biochemical, physiological, pharmacological, and behavioral profiles suggest that it could play a key role in the addiction process. For instance, genomic studies in humans have suggested a link between variants in the gene encoding the 5-HT7 receptor and alcoholism. Recent behavioral testing using high-affinity antagonists in mice and preliminary tests with alcohol-preferring rats suggest that this receptor could mediate alcohol consumption and/or reinforcement and play a role in seeking/craving behavior. Interest in the development of new and more selective pharmacological agents for this receptor will aid in examining the 5-HT7 receptor as a novel target for treating addiction.

Highlights

The neurotransmitter serotonin (5-HT) plays a major a role in a number behavioral and psychophysiological functions such as behavioral inhibition, appetite regulation, mood, cognitive functions, thermoregulation, and addictive behaviors
Double labeling for 5-HT7 receptor (5-HT7R) and tyrosine hydroxylase (DA marker) showed that 5-HT7Rs do not appear to be located on DA neurons, whereas double immunolabeling for 5-HT7Rs and glial fibrillary acidic protein (GFAP a marker of astrocytes) or tryptophan hydroxylase (5-HT marker) showed that 5-HT7Rs are located on glia and serotonergic cells (Parga et al, 2007). These results suggest that 5-HT7Rs are involved in regulating DA neuronal development following elimination of 5-HT neurons or a reduction of 5-HT levels (Parga et al, 2007). 5-HT7Rs are involved in DA neuronal firing activity and DA release
The high responders (HR) rats had significantly lower 5htr7 gene expression in the dorsal hippocampus, intralaminar nucleus, and paraventricular thalamic nucleus than the low responders (LR) rats (Ballaz et al, 2007a). These results suggest that the low expression of 5htr7 mRNA in HR rats may be involved in increased novelty seeking behavior (Hedlund, 2009)

Summary

Introduction

The neurotransmitter serotonin (5-HT) plays a major a role in a number behavioral and psychophysiological functions such as behavioral inhibition, appetite regulation, mood, cognitive functions, thermoregulation, and addictive behaviors. These studies suggest that activation of 5-HT7Rs may be involved in early neuronal development of the DAergic system and may regulate DA release within the MCL-DA system.

Results

Conclusion