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