The discovery by Albert Hofmann more than fifty years ago of the hallucinogenic effects of LSD irreversibly altered the course of both biological psychiatry and popular culture. Hallucinogens of all types are subject to widespread and increasing abuse by adolescents and young adults in this country. For example, in 1998 use of hallucinogens exceeded that of cocaine in the age groups 12-17 and 18-25. Indeed, hallucinogens were more commonly ingested than tranquilizers, inhalants, and sedatives combined. Furthermore, LSD was identified in 1999 as a """"""""club drug"""""""" in the campaign by the National Institute on Drug Abuse to alert the public to the hazards of these agents. In addition to the well recognized abuse liability of these drugs, hallucinogens are perhaps unique in that an understanding of their mechanisms of action would contribute not only to an amelioration of the burdens of illicit use but might also provide a key to solving the puzzle of psychosis, another major human affliction. The present investigations seek to characterize indoleamine hallucinogens such as LSD and phenethylamine hallucinogens as exemplified by DOM in combined behavioral, biochemical, and analytical [GC-MS] studies. Specifically, studies will also examine the neuroanatomical sites involved in hallucinogen- induced stimulus control. In addition, experiments will further characterize interactions between the serotonergic and glutamatergic systems in the brain. Finally, the mechanisms responsible for the potentiation of LSD and other hallucinogens by fluoxetine and related selective serotonin reuptake inhibitors will be examined. Taken together, the correlational use of powerful methods for the assessment of in vivo and in vitro efficacy and of brain levels of DOM and of neurotransmitters will provide new understanding of the mode of action of hallucinogens.
| Winter, J C; Amorosi, D J; Rice, Kenner C et al. (2011) Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice. Pharmacol Biochem Behav 99:311-5 |
| Krall, C M; Richards, J B; Rabin, R A et al. (2008) Marked decrease of LSD-induced stimulus control in serotonin transporter knockout mice. Pharmacol Biochem Behav 88:349-57 |
| Reissig, C J; Eckler, J R; Rabin, R A et al. (2008) The stimulus effects of 8-OH-DPAT: evidence for a 5-HT2A receptor-mediated component. Pharmacol Biochem Behav 88:312-7 |
| Winter, J C (2008) Antagonism of phencyclidine-induced stimulus control in the rat by other psychoactive drugs. Pharmacol Biochem Behav 88:189-95 |
| Winter, J C; Rice, K C; Amorosi, D J et al. (2007) Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 87:472-80 |
| Acheson, Ashley; Farrar, Andrew M; Patak, Michele et al. (2006) Nucleus accumbens lesions decrease sensitivity to rapid changes in the delay to reinforcement. Behav Brain Res 173:217-28 |
| Reissig, C J; Eckler, J R; Rabin, R A et al. (2005) The 5-HT1A receptor and the stimulus effects of LSD in the rat. Psychopharmacology (Berl) 182:197-204 |
| Winter, J C; Eckler, J R; Rice, K C et al. (2005) Serotonergic/glutamatergic interactions: potentiation of phencyclidine-induced stimulus control by citalopram. Pharmacol Biochem Behav 81:694-700 |
| Doat-Meyerhoefer, M M; Hard, R; Winter, J C et al. (2005) Effects of clozapine and 2,5-dimethoxy-4-methylamphetamine [DOM] on 5-HT2A receptor expression in discrete brain areas. Pharmacol Biochem Behav 81:750-7 |
| Winter, J C; Kieres, A K; Zimmerman, M D et al. (2005) The stimulus properties of LSD in C57BL/6 mice. Pharmacol Biochem Behav 81:830-7 |
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