The goal of this project is to use rodent models to elucidate the mechanisms underlying the behavioral effects of hallucinogenic drugs of abuse, including LSD and DOI,as well as natural products used in recreational, ritual, or religious contexts, including SMeODMT and Ayahuasca tea. Based on the profound effects of hallucinogens on responses to sensory and emotional stimuli, behavioral effects will be measured using a multivariate profile of exploratory and investigatory behavior provided by rat and mouse Behavioral Pattern Monitor systems. These computerized systems assess activity, exploration, and behavioral organization - three major aspects of rodent behavior in an open field. The project has two specific aims.
The first aim i s to characterize and identify the specific mechanisms by which LSD and synthetic equivalents of Ayahuasca (""""""""Pharmahuasca"""""""") alter exploratory behavior in rats. These studies will extend initial investigations into the nature of the biphasic, LSD-like profile of Pharmahuasca, in which exploratory behavior is initially suppressed and then increases as time progresses. We will test whether metabolic interactions between Pharmahuasca components contribute to the LSD-like behavioral profile, or whether specific neurochemical or receptor interactions are involved.
The second aim i s to assess the respective contributions of 5HT1A and 5HT2A serotonin receptors to the effects of hallucinogens on exploratory and investigatory behavior in mice. Both selective antagonists and knockouts of 5HTIA and 5HT2A receptors will be studied in order to develop converging evidence to test the hypothesis that both receptors contribute to the behavioral effects. This research is designed to elucidate the neurobiological mechanisms responsible for the acute effects of hallucinogens, which are presumably responsible for the recreational use of these drugs of abuse. These studies should also further our basic understanding of the behavioral functions of serotonergic systems. Collectively, this work is consistent with the stated mission of NIDA to bring """"""""thepower of science to bear on drug abuse and addiction."""""""" Additionally, the study of psychoactive properties of natural products has been identified by NIDA as a priority area for research. Relevance: The recreational use of hallucinogens is a concern from a public health standpoint. This work will further our understanding of the basic neural mechanisms mediating the behavioral effects of these drugs of abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA025412-02
Application #
7840478
Study Section
Special Emphasis Panel (ZRG1-F02A-C (20))
Program Officer
Avila, Albert
Project Start
2009-05-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$52,154
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Halberstadt, Adam L; Geyer, Mark A (2013) Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement. Psychopharmacology (Berl) 227:727-39
Halberstadt, Adam L; Powell, Susan B; Geyer, Mark A (2013) Role of the 5-HTýýýA receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice. Neuropharmacology 70:218-27
Tanaka, Shoji; Young, Jared W; Halberstadt, Adam L et al. (2012) Four factors underlying mouse behavior in an open field. Behav Brain Res 233:55-61
Halberstadt, Adam L; Buell, Mahalah R; Price, Diana L et al. (2012) Differences in the locomotor-activating effects of indirect serotonin agonists in habituated and non-habituated rats. Pharmacol Biochem Behav 102:88-94
Halberstadt, Adam L; Nichols, David E; Geyer, Mark A (2012) Behavioral effects of ýý,ýý,ýý,ýý-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor. Psychopharmacology (Berl) 221:709-18
Halberstadt, Adam L; Lehmann-Masten, Virginia D; Geyer, Mark A et al. (2011) Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice. Psychopharmacology (Berl) 215:81-92
van den Buuse, Maarten; Ruimschotel, Emma; Martin, Sally et al. (2011) Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia. Neuropharmacology 61:209-16
Halberstadt, Adam L; Geyer, Mark A (2011) Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology 61:364-81
Halberstadt, Adam L; Koedood, Liselore; Powell, Susan B et al. (2011) Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice. J Psychopharmacol 25:1548-61
Halberstadt, Adam L; Geyer, Mark A (2010) LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor. Psychopharmacology (Berl) 208:179-89

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