Optogenetic inhibition of cocaine seeking in rats.
paper
Cited
Public
- Authors
- Stefanik, Michael T; Moussawi, Khaled; Kupchik, Yonatan M; Smith, Kyle C; Miller, Rachel L; Huff, Mary L; Deisseroth, Karl; Kalivas, Peter W; LaLumiere, Ryan T
- Year
- 2013
- Journal
- Addiction biology
- PMID
- 22823160
- DOI
- 10.1111/j.1369-1600.2012.00479.x
- PMCID
- PMC3578202
Inhibitory optogenetics was used to examine the roles of the prelimbic cortex (PL), the nucleus accumbens core (NAcore) and the PL projections to the NAcore in the reinstatement of cocaine seeking. Rats were microinjected into the PL or NAcore with an adeno-associated virus containing halorhodopsin or archaerhodopsin. After 12 days of cocaine self-administration, followed by extinction training, animals underwent reinstatement testing along with the presence/absence of optically induced inhibition via laser light. Bilateral optical inhibition of the PL, NAcore or the PL fibers in the NAcore inhibited the reinstatement of cocaine seeking.
Histological and electrophysiological verification of the opsin expression and inhibition of reinstated cocaine seeking. (aβ) eNpHR3.0-YFP expression (green) after virus injection into the prelimbic cortex (PL). Dashed lines indicate approximate boundaries of the PL. (aββ) Laser-mediated hyperpolarization and inhibition of firing in a single eNpHR3.0-infected pyramidal cell. (aβββ) Laser light in the PL suppressed cocaine + cue-induced reinstated behavior. (bβ) eNpHR3.0-YFP expression in the nucleus accumbens core (NAcore) after virus injection into the NAcore. ac, anterior commissure. *Area of relatively low fluorescence corresponding to the location of the fiber optic. (bββ) Laser-mediated hyperpolarization and inhibition of firing of a single eNpHR3.0-infected medium spiny cell. (bβββ) Laser light into the NAcore suppressed reinstated behavior. (cβ) Immunostaining of archaerhodopsin expression in axonal fibers the NAcore after virus injection into the PL. (cββ) Optical inhibition of field potentials recorded in NAcore after electrical stimulation in the eNpHR3.0-infected PL of a rat. Units of laser intensity are arbitrary and correspond to step increases until the field potential disappeared and remained at this intensity for the duration of the experiment. (cβββ) Laser illumination in the NAcore suppressed both cocaine- and cocaine + cue-induced reinstatement.
1β11 of 11
| Name | Type |
|---|---|
| 561 nm light local | drug |
| ArchT local | drug |
| cocaine | phenotype |
| Cocaine + cue-primed reinstatement local | phenotype |
| cocaine-induced locomotor activity local | phenotype |
| Cocaine-primed reinstatement local | phenotype |
| control virus | drug |
| cue-induced reinstatement | phenotype |
| cue-reinstated cocaine seeking local | phenotype |
| drug-seeking behavior | phenotype |
| eNpHR3.0 local | drug |
| fibers | drug |
| Field potential amplitude local | phenotype |
| inactive lever presses local | phenotype |
| inactive lever pressing | phenotype |
| Laser illumination local | drug |
| laser stimulation local | drug |
| locomotor activity | phenotype |
| nucleus accumbens core | anatomy |
| open-field behavior local | phenotype |
| Open-field testing local | phenotype |
| optical inhibition local | drug |
| paraformaldehyde | drug |
| PL-NAcore projection local | anatomy |
| prelimbic cortex | anatomy |
| rAAV2-CAG-ArchT-GFP local | drug |
| rAAV2-hSyn-eNpHR3.0-EYFP local | drug |
| rAAV5-CMV-GFP local | drug |
| rAAV5-hSyn-EYFP local | drug |
| rats | cohort |
| reinstated drug seeking local | phenotype |
| reinstatement | phenotype |
| Sprague-Dawley rats | cohort |
| yellow fluorescent protein local | drug |
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