The proposed investigation seeks to characterize and distinguish a group of drugs of abuse in terms of their properties as discriminative stimuli. Emphasis will be upon hallucinogens of the indoleamine/phenethylamine type including lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4- methylamphetamine (DOM). All drugs studied behaviorally also will be examined in terms of their binding characteristics at serotonergic and adrenergic receptors. initially, binding will be quantitated at the 5- HT1A. 5-HT1B, 5-HT1C, and 5-HT2 subtypes of the serotonergic receptor and at the alpha and beta adrenergic receptors. Nearly all drugs of abuse are able to assume stimulus control in animals. This fact provides a sensitive and informative approach to the study of the mechanisms of action of a variety of drugs habitually chosen for non- medical use by humans. Complementing discrimination methods, receptor binding techniques provide a unique opportunity to assess the molecular events which underlie specific behavioral effects. Thus, receptor binding and behavioral experiments will be conducted in parallel. The latter will provide evidence either for or against functional significance of a given receptor site. A long-term objective of the proposed research is to achieve an understanding of these complex behavioral effects in biochemical terms and thus to facilitate rational clinical intervention.
| 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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