William E. Fantegrossi, Ph.D.

WEFantegrossi@uams.edu

Research conducted in my lab focuses on the in vivo pharmacology of serotonergic drugs of abuse. We are particularly interested in “emerging” street drugs, including designer hallucinogens and MDMA analogues. Rodent models of drug discrimination, intravenous drug self-administration, locomotor activity, PET neuroimaging and assays of drug-elicited behavior are employed in order to better understand the neuropharmacology of these drugs of abuse, as well as to probe biological mechanisms of drug dependence. Non-human primate models of intravenous drug self-administration and PET neuroimaging are also used in order to study the persistent effects of abused drugs on neurochemistry and behavior. Efforts to establish ex vivo and in vivo assays for the identification of agonist-specific signaling and inverse agonist efficacy at serotonin 5-HT2A receptors are also underway.

Telemetry graphic

Telemetry – Mice are surgically implanted with glass-encapsulated biotelemetry probes under ketamine and xylazine anesthesia. Probes simultaneously measure core temperature and locomotor activity and relay these data to receivers connected to a PC. Receivers are housed within light- and sound-attenuating temperature controlled enclosures, where ambient temperature is held at 20 or 29 degrees Celsius for the duration of all experiments. Injection of 10.0 mg/kg MDMA disrupts murine thermoregulation such that drug administration in a cool ambient environment leads to hypothermia, while drug administration in a warm ambient environment leads to hyperthermia. The locomotor stimulant effects of MDMA are identical at 20 and 29 degrees Celsius.

 

Early scan

Early scan – Mice are transported to the micro PET facility, anesthetized with inhaled isoflurane and positioned within the PET camera. Subjects are then injected with 10.0 mg/kg nantenine or vehicle. Ten minutes later, [11C]nantenine is injected as an IV bolus via tail vein, and the scan begins. At early time points after infusion of [11C]nantenine, specific activity is detected in the brain of the control animal, but not the subject pre-treated with unlabeled nantenine.

Late scan

Late scan – At later time points, [11C]nantenine washes out of the brain of the unblocked control animal. High levels of activity in the liver suggest metabolism of [11C]nantenine.

Selected Publications

Weerts EM, Fantegrossi WE, Goodwin AK: The value of nonhuman primates in drug abuse research. Exp. Clin. Psychopharmacol. 15:309-27, 2007.

Yarosh HL, Katz EB, Coop A, Fantegrossi WE: MDMA-like behavioral effects of N-substituted piperazines in the mouse. Pharmacol. Biochem. Behav. 88:18-27, 2007.

Kalechstein AD, De La Garza R, Mahoney JJ, Fantegrossi WE, Newton TF: MDMA use and neurocognition: a meta-analytic review. Psychopharmacology 189:531-537, 2007.

Fantegrossi WE: Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity? Psychopharmacology 189:471-82, 2007.