Do 5-HT7R Antagonists have Anti-Cocaine Effects?

Substance abuse costs the United States over $740 billion annually in healthcare, law enforcement, rehabilitation, and decreased work productivity costs. While there are certain clinical treatments for nicotine, opioid, and alcohol addiction, there is yet an equivalent treatment for psychostimulant addiction. The 5-HT7 receptor (5-HT7R) is one of the more recently discovered members of the serotonin receptor family. The involvement of 5-HT7Rs in thermoregulation, memory, and circadian rhythms, suggests that the receptor also plays a role in mood regulation, making it a potential target in the treatment of psychiatric disorders. Given’ the distribution of the 5-HT7Rs in the brain and its known cellular functions, the receptor has also been implicated in addiction processes. Most studies to date have mainly focused on psychiatric conditions like depression, having yet to explore the role of 5-HT7Rs in psycho-stimulant behaviors. In our study, the effects of SB 269970(SB), a selective antagonist for 5-HT7Rs, were tested on 8-OH-DPAT induced hypothermia, cocaine-induced locomotion, and fos expression in the nucleus accumbens. We found that SB effectively reversed 8-OH-DPAT induced hypothermia, indicating the drug is indeed binding to the 5-HT7R. However, while cocaine did increase locomotor activity and fos expression in the nucleus accumbens in rats, SB had no effect on either measure. These results suggest that 5-HT7Rs may work through pathways other than motor and should be explored through additional behavioral tests. Other brain regions should also be studied for fos expression to see if there is a region-specific effect of 5-HT7Rs and fos expression. The efficacy of SB to 5-HT7Rs and results of past studies on the drug suggests its potential as a pharmacological treatment for psychostimulant disorders.