This application studies the effects of intravenous cocaine administration in the brains of rats conditioned to cocaine, with in vivo hemodynamic measurement cross-referenced with c-fos immunoreactivity. The nemodynamic measurements are made using functional magnetic resonance imaging (fMRI), which infers oatterns of brain activity from stimulation-induced changes in the magnetic relaxivity of the local blood and issue. This method is well-established in rat models of somatosensory stimulation, and increasingly popular for analyzing the acute effects of psychoactive drugs. The specificity of the most popular pharmacological MRI method, cerebral blood volume (CBV) imaging with an injected contrast agent, is assessed using the jxtinction-reinstatement rat model of compulsive cocaine abuse. The effects of popular anesthesia treatments on drug-primed relapse behavior and neuronal Fos expression are assessed before fMRI experiments. The goal of this research is to conclusively separate the loci of cocaine-induced neural activity from non-specific cerebrovascular effects in a paradigm that preserves drug-primed reinstatement behavior, which would produce a fMRI-compatible small animal model of cocaine craving and relapse. ? ? ?
Kufahl, Peter R; Peartree, Natalie A; Heintzelman, Krista L et al. (2015) Region-specific effects of isoflurane anesthesia on Fos immunoreactivity in response to intravenous cocaine challenge in rats with a history of repeated cocaine administration. Brain Res 1594:256-66 |
Bastle, Ryan M; Kufahl, Peter R; Turk, Mari N et al. (2012) Novel cues reinstate cocaine-seeking behavior and induce Fos protein expression as effectively as conditioned cues. Neuropsychopharmacology 37:2109-20 |
Kufahl, Peter R; Zavala, Arturo R; Singh, Akanksha et al. (2009) c-Fos expression associated with reinstatement of cocaine-seeking behavior by response-contingent conditioned cues. Synapse 63:823-35 |
Kufahl, Peter R; Pentkowski, Nathan S; Heintzelman, Krista et al. (2009) Cocaine-induced Fos expression is detectable in the frontal cortex and striatum of rats under isoflurane but not alpha-chloralose anesthesia: implications for FMRI. J Neurosci Methods 181:241-8 |