Animal Models of Serotonergic Psychedelics

 

            The major target of hallucinogenic drugs (LSD, psilocybin, mescaline) has been found to be the serotonin 5-HT_2A receptor. In stimulating this receptor, changes in perception, cognition, emotion, and sensory processing occur. Humans are much more complex in these areas than other animal models, which raises questions about the accurateness of the findings within current drug experiments that utilize animals such as rodents. Firstly, questions of ego and spiritual experiences are unanswered when under the influence of the drug without verbal communication. Secondly, the sensory systems are quite different from mouse to human, which poses more difficulty in understanding how these drugs affect sensory stimulation. Despite these differences, rodents remain amongst the best subjects for such experimental research.

            To circumvent some of these problems, “one of the priorities in molecular pharmacology research is to determine which behaviors in rodents predict specific types of neuropsychological effects in humans.” For example, head-twitch behavior in mice is used in the prediction of psychedelic behavior in humans. Other types of behavior were also examined, and these include, pauses on fixed-ratio schedules of reinforcement, locomotor response and exploratory behavior, prepulse inhibition of startle, anxiety, impulsivity and response inhibition, time perception, and memory.

            It was concluded that other than head-twitch response, drug discrimination, pauses on fixed-ratio schedules of reinforcement, and alterations in time perception proved to be valuable tools to predict psychedelic potential in humans. Prepulse inhibition of startle, changes in locomotor response and exploratory behavior, and perception of time also seemed to be affected while under the influence of psychadelics as well as dissociatives, and deliriants. However, a comparison of these behaviors to those in a human is still under debate. The article comments, “We look forward to models that will be used for unraveling the neurochemical events that converge on shared patterns of behavioral alterations, or distinguish those that differ.” Understanding the neuronal receptor-signaling mechanisms under the influence of psychedelic drugs may also lead to a better understanding in endogenous psychoses such as schizophrenia.

           

http://pubs.acs.org/doi/full/10.1021/cn300138m