Dr. Rita Fuchs-Lokensgard
Biographical Information

Pilot Grant - Neural Substrates of Relapse to Cocaine Seeking Produced by Drug-Associated Contextual Stimuli

The proposed experiments tested the hypothesis that separate neural substrates mediate cocaine relapse elicited by drug-associated contextual stimuli versus explicit conditioned stimuli (CSs) and cocaine. Specifically, we investigated the involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), nucleus accumbens core (NACc), dorsolateral caudate putament (dlCPu), and dorsomedial prefrontal cortex (dmPFC) in contextual reinstatement of cocaine-seeking behavior, the involvement of the dlCPu in explicit CS-induced reinstatement, and the involvement of the DH in explicit CS- and cocaine-induced reinstatement. 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 responses) was assessed in the cocaine-paired context, in an alternate context, in the presence of the explicit CSs, or following cocaine priming (10 mg/kg, i.p.). DH inactivation abolished contextual, but failed to alter explicit CS- or cocaine-induced, reinstatement of cocaine-seeking behavior. BLA, NACc, or dmPFC inactivation also abolished contextual reinstatement. Inactivation of the dlCPu abolished both contextual and explicit CS-induced reinstatement. Conversely, inactivation of the control brain regions failed to alter contextual reinstatement. In conclusion, the dlCPu, NACc, BLA, DH and dmPFC play critical roles in contextual reinstatement. Previous and the present findings suggest that the BLA and dlCPu are critical for explicit CS-induced, but not cocaine-primed, reinstatement and the NACc and dmPFC are critical for both explicit CS-induced and cocaine-primed reinstatement. Thus, distinct but partially overlapping neural substrates mediate context-induced, explicit CS-induced, and cocaine-primed reinstatement of extinguished cocaine-seeking behavior.