Serotonergic modulation of habituation and associative learning in mice

Abstract

Psychedelic drugs are frequently used in therapy-related scenarios where they can have a long-term effect on mood and psychiatric issues such as depression and anxiety. Psychedelics are also used in relation to hearing, because they can influence perception of auditory stimuli. 2,5-Dimethoxy-4-iodoamphetamine, also known as DOI, is a psychedelic drug with effects on associative learning. In this experiment, ketanserin and saline are used as well. Ketanserin specifically is an antagonist and it’s believed to block the effects of the agonist DOI. Saline is used as a control to compare results amongst the different drugs. To investigate, we studied the effects of the serotonergic psychedelic drug, DOI, to assess its effects on habituation and associative learning during pre-pulse inhibition (PPI) of the acoustic startle response (ASR) in mice. ASR is a phenomenon where mice jump when exposed to a sudden stimulus. PPI is when a ‘warning noise’ will be played to prime the mice for a sudden, loud noise. Effects of ketanserin and saline during PPI and ASR were studied as well. The data showed that the dosage of DOI did not contribute to differences in ASR or PPI. Additionally, DOI correlates with a lower startle response with higher ISI’s, indicating associative learning and habituation. Ketanserin temporarily blocked habituation during two sessions, but others remained the same. In the saline sessions, habituation was shown. From these results, we can conclude that DOI may improve associative learning indicated by the changes in PPI with long ISI’s. Additionally, in the future, this experiment can be redone with a larger batch of mice to ensure that the results are accurate.