Department of Neuroscience
Rita Fuchs-Lokensgard, Ph.D.
University of North Carolina at Chapel Hill
Phone: (919) 843-9112
2000: Ph.D. Psychology, Arizona State University (Cognitive and Behavioral Systems, Behavioral Neuroscience Program)
1997 M.A. Psychology, Arizona State University (Cognitive and Behavioral Systems, Behavioral Neuroscience Program)
1995 B.S. Psychology, Summa Cum Laude, Arizona State University
Neural Substrates of Relapse to Cocaine Seeking Produced by Drug-Associated Contextual Stimuli
The pilot grant aimed to test the hypothesis that separate neural substrates mediate cocaine relapse elicited by drug-associated contextual stimuli versus explicit conditioned stimuli (CSs). Specifically, in the proposed pilot experiments and subsequent studies funded by a NIDA R01 and the NARC Animal core, we investigated the involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), nucleus accumbens core (NACc), nucleus accumbens shell (NACs), dorsolateral caudate putament (dlCPu), and dorsomedial prefrontal cortex (dmPFC) in contextual reinstatement of cocaine-seeking behavior. We also investigated the involvement of several anatomical control brain regions, including the ventromedial prefrontal cortex (vmPFC), the barrel fields region of the somatosensory cortex (SSbf), and the trunk region of the somatosensory cortex (SStr), in contextual reinstatement. Rats were trained to self-administer cocaine in a distinct context or in the presence of CSs paired explicitly with cocaine infusions. Responding was then extinguished. Subsequently, the target brain regions or anatomical control regions were functionally inactivated using tetrodotoxin (0 or 5 ng/µl) or a combination of baclofen and muscimol (1.0/0.1 mM), and cocaine-seeking behavior (i.e., nonreinforced lever responses) was assessed in the cocaine-paired context or in an alternate context. These experiments revealed that the DH and NACs play selective roles in context-induced reinstatement, whereas the BLA, dlCPu, NACc, and dmPFC are critical for both explicit CS-induced and context-induced reinstatement. Thus, distinct but partially overlapping neural substrates mediate reinstatement of extinguished cocaine-seeking behavior depending on stimulus type.
Publications Arising from Pilot Project:
NIDA R01 DA17673-01A1 “Neural bases of drug context-induced cocaine seeking”
PI: Fuchs Lokensgard RA; Project Period: 2/5/05-1/31/10
Fuchs, R.A., Ramirez, D.R., and Bell, G.H. (2008). Nucleus accumbens shell and core involvement in drug context-induced reinstatement of cocaine seeking in rats. Submitted to Psychopharmacology, [Epub ahead of print]
Fuchs, R.A., Eaddy, J.L., Su, Z.-I., Bell, G. (2007). Interactions of the basolateral amygdala with the dorsal hippocampus and dorsomedial prefrontal cortex regulate drug-context-induced cocaine seeking in rats. European Journal of Neuroscience, 26:487-498.
Fuchs, R.A., Branham, R.K., and See, R.E. (2006). Different neural substrates mediate cocaine seeking following abstinence versus extinction training: A critical role for the dorsolateral caudate-putamen. Journal of Neuroscience, 26:3584-3588.
Fuchs, R.A., Evans, K.A., Ledford, C.C., and See, R.E. (2004). The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats. Neuropsychopharmacology, 30:296-309.