Addiction to cocaine results in a number of long-term behavioral changes. Particularly insidious is the development of craving for the drug during abstinence. Craving is a primary cause of relapse, and to date little information is available on the neural substrates that mediate the behavioral expression of craving. This research proposal attempts to address this lacuna in our understanding. It is hypothesized that the repeated exposure to cocaine progressively augments the activity of corticofugal glutamatergic efferents to the nucleus accumbens, and that this excitatory input initiate both drug- and environmentally-induced craving for cocaine. To test this hypothesis, rats will be trained to self- administered intravenous cocaine. Once stable levels of self- administration are achieved, the behavior will be extinguished and aspects of the neural basis of the reinstatement of cocaine-seeking behavior will be examined.. Reinstatement will be induced by 1) the microinjection of glutamatergic drugs into the nucleus accumbens, 2) systemic cocaine in rats pretreated with drugs into the nucleus accumbens, 3) the presentation of conditioned cues after pretreatment with glutamatergic drugs, and electrical stimulation drugs, and 4) electrical stimulation of cortical regions providing glutamatergic afferents to the nucleus accumbens. In addition, microdialysis will be employed to estimate changes in glutamate transmission in the nucleus accumbens following cocaine or cue-induced reinstatement.
| Neuhofer, Daniela; Kalivas, Peter (2018) Metaplasticity at the addicted tetrapartite synapse: A common denominator of drug induced adaptations and potential treatment target for addiction. Neurobiol Learn Mem 154:97-111 |
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| Spencer, Sade; Neuhofer, Daniela; Chioma, Vivian C et al. (2018) A Model of ?9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens. Biol Psychiatry 84:601-610 |
| Bobadilla, Ana-Clara; Heinsbroek, Jasper A; Gipson, Cassandra D et al. (2017) Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior. Prog Brain Res 235:93-112 |
| Spencer, Sade; Kalivas, Peter W (2017) Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse. Int J Neuropsychopharmacol 20:797-812 |
| Kupchik, Yonatan M; Kalivas, Peter W (2017) The Direct and Indirect Pathways of the Nucleus Accumbens are not What You Think. Neuropsychopharmacology 42:369-370 |
| Smith, Alexander C W; Scofield, Michael D; Heinsbroek, Jasper A et al. (2017) Accumbens nNOS Interneurons Regulate Cocaine Relapse. J Neurosci 37:742-756 |
| Brown, Robyn Mary; Kupchik, Yonatan Michael; Spencer, Sade et al. (2017) Addiction-like Synaptic Impairments in Diet-Induced Obesity. Biol Psychiatry 81:797-806 |
| Bobadilla, Ana-Clara; Garcia-Keller, Constanza; Heinsbroek, Jasper A et al. (2017) Accumbens Mechanisms for Cued Sucrose Seeking. Neuropsychopharmacology 42:2377-2386 |
| Spencer, Sade; Garcia-Keller, Constanza; Roberts-Wolfe, Douglas et al. (2017) Cocaine Use Reverses Striatal Plasticity Produced During Cocaine Seeking. Biol Psychiatry 81:616-624 |
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