Effect of Hallucinogens on Unconditioned Behavior

  • Adam L. HalberstadtEmail author
  • Mark A. Geyer
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 36)


Because of the ethical and regulatory hurdles associated with human studies, much of what is known about the psychopharmacology of hallucinogens has been derived from animal models. However, developing reliable animal models has proven to be a challenging task due to the complexity and variability of hallucinogen effects in humans. This chapter focuses on three animal models that are frequently used to test the effects of hallucinogens on unconditioned behavior: head twitch response (HTR), prepulse inhibition of startle (PPI), and exploratory behavior. The HTR has demonstrated considerable utility in the neurochemical actions of hallucinogens. However, the latter two models have clearer conceptual bridges to human phenomenology. Consistent with the known mechanism of action of hallucinogens in humans, the behavioral effects of hallucinogens in rodents are mediated primarily by activation of 5-HT2A receptors. There is evidence, however, that other receptors may play secondary roles. The structure–activity relationships (SAR) of hallucinogens are reviewed in relation to each model, with a focus on the HTR in rats and mice.


Psychedelic Wet dog shake 5-HT2C receptor Lisuride Quipazine Lysergic acid diethylamide LSD DOI SB-242,084 M100907 Mescaline Psilocybin Locomotor activity 25I-NBOMe 25CN-NBOH 1-methylpsilocin Rat Mouse 



This work was supported by grants from NIDA (R01 DA002925 and R01 DA041336), NIMH (K01 MH100644), and the Veteran’s Affairs VISN 22 MIRECC.


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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of California San DiegoLa JollaUSA
  2. 2.Research ServiceVA San Diego Healthcare SystemSan DiegoUSA

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