Serotonin Study in Rats Furthers Medical Research
Serotonin is a neurotransmitter linked to aggression, depression, and neuropsychiatric disorders such as schizophrenia. This summer, Anisha Bhanot ’13, Marla Marquez ’14 and Bridget Fitzpatrick ’13 conducted research on two serotonin receptor subtypes in male rats with regard to how different drugs affect each type of receptor. They worked under Douglas Weldon, the Stone Professor of Psychology and director of the Neuroscience Program.
Fitzpatrick’s summer research was funded through the Edward and Virginia Taylor Fund for Student/Faculty Research in Chemistry, established in 2008 through a gift from Ted ’46 and Virginia to inspire students interested in chemical research and to facilitate their work with outstanding faculty.
The two receptors that the group dealt with are serotonin (5-Hydroxytryptamine, or 5-HT) 1A and 1B, or 5-HT1A and 5-HT1B. The drugs that the students administered served either as agonists or antagonists to the receptors; agonists activate the receptor, while antagonists block agonist-mediated effects.
Bhanot’s project explored the “Role of Serotonin Receptor Subtypes 1A and 1B in Prepulse Inhibition Modulation of the Acoustic Startle Response.” The acoustic startle response (ASR) is the response to abrupt auditory stimuli, while prepulse inhibition (PPI) is the reduction in startle response when a non-startling stimulus (prepulse) precedes a startling stimulus (startle pulse). Serotonin receptor subtypes 1A and 1B are believed to play a role in the modulation of PPI. Anpirtoline, a drug that Bhanot is working with, is considered a 1B agonist. Bhanot’s project examined whether anpirtoline causes opposite effects at 1A and 1B receptors in male rats.
Weldon’s previous research shows that anpirtoline produces a decrease in ASR and affects PPI in male rats. In addition, other studies have suggested that 1A agonists produce opposite effects of 1B agonists in mice. Bhanot combined anpirtoline with WAY 100635, a 1A antagonist, and tested the hypothesis that the combination of anpirtoline and WAY 100635 would produce a greater reduction in ASR and PPI than either anpirtoline or WAY 100635 alone.
In support of the hypothesis, Bhanot found that treatment with the combination of anpirtoline and WAY 100635 reduced startle and PPI when compared with control rats or rats given either drug alone. Her project proposes that anpirtoline’s effects of stimulating 1B receptors may be masked by its effects of stimulating 1A receptors.
The findings of this study are significant since many patients diagnosed with several neuropsychiatric disordered show signs of PPI deficits. The results of the Bhanot’s project may provide further insight into the neural underpinnings behind such disorders.
Fitzpatrick and Marquez’s research dealt with the Frustration Effect and the 5-HT1A receptor in rats for their project, “Effect of Serotonin 1A Receptor Stimulation on Frustration.” They began by training rats to run through a double-runway maze in order to earn a reward, in this case a specified number of chocolate pellets in each goal box of the maze. When the rats successfully run through the first runway of the maze but do not obtain a reward in the first goal box, they become frustrated. The result of this Frustration Effect is an increase in drive and motivation that causes the rat to run faster along Runway 2.
Serotonin 5-HT1A agonists have been found to reduce aggression and impulsivity. Therefore, the group hypothesized that it also serves to reduce frustration, and will thus prevent the increase in running speed typically seen as a result of nonreward. In their study, Marquez and Fitzpatrick administered the drug 8-hydroxy-2-(di-n-propylamino) tetralin, or 8-OHDPAT, which is a 5-HT1A agonist, and they expected this drug to reduce the Frustration Effect when the unrewarded rats run along runway 2. They found an observable Frustration Effect in Runway 2 due to nonreward. Additionally, they saw a dose dependent effect of the 8-OHDPAT that, at the highest dose, appeared to eliminate the presence of a Frustration Effect.
Serotonin may help unlock key information in the treatment of schizophrenia. Weldon’s summer research team helped to further the current knowledge about serotonin receptors in rats, which may be useful to medical research in the future.
All three students are neuroscience majors. Outside the lab, Fitzpatrick takes part in the figure skating club, Bhanot is a site coordinator for HAVOC, and Marquez is a member of the dance team.
Bridget Fitzpatrick is a graduate Needham High School (Mass.); Anisha Bhanot graduated from Portsmouth High School (N.H.); Marla Marquez is a graduate of Coral Gables Senior High School (Fla.).