Victória A Müller Ewald1,2, Benjamin J De Corte3,4, Subhash C Gupta5, Katherine V Lillis6, Nandakumar S Narayanan3,4,7, John A Wemmie3,5,7, Ryan T LaLumiere3,6,7. 1. Interdisciplinary Neuroscience Program, University of Iowa, Iowa City, IA, 52242, USA. victoriaaugusta-mullerewald@uiowa.edu. 2. W311 Seashore Hall, Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, 52242, USA. victoriaaugusta-mullerewald@uiowa.edu. 3. Interdisciplinary Neuroscience Program, University of Iowa, Iowa City, IA, 52242, USA. 4. Department of Neurology, University of Iowa, Iowa City, IA, 52242, USA. 5. Department of Psychiatry, University of Iowa, Iowa City, IA, 52242, USA. 6. W311 Seashore Hall, Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, 52242, USA. 7. Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA.
Abstract
RATIONALE: The infralimbic cortex (IL) and its downstream projection target the nucleus accumbens shell (NAshell) mediate the active suppression of cocaine-seeking behavior. Although an optogenetic approach would be beneficial for stimulating the IL and its efferents to study their role during reinstatement of cocaine seeking, the use of channelrhodopsin introduces significant difficulties, as optimal stimulation parameters are not known. OBJECTIVES: The present experiments utilized a stable step-function opsin (SSFO) to potentiate endogenous activity in the IL and in IL terminals in the NAshell during cocaine-seeking tests to determine how these manipulations affect cocaine-seeking behaviors. METHODS: Rats first underwent 6-h access cocaine self-administration followed by 21-27 days in the homecage. Rats then underwent cue-induced and cocaine-primed drug-seeking tests during which the optogenetic manipulation was given. The same rats then underwent extinction training, followed by cue-induced and cocaine-primed reinstatements. RESULTS: Potentiation of endogenous IL activity did not significantly alter cue-induced or cocaine-primed drug seeking following the homecage period. However, following extinction training, enhancement of endogenous IL activity attenuated cue-induced reinstatement by 35% and cocaine-primed reinstatement by 53%. Stimulation of IL terminals in the NAshell did not consistently alter cocaine-seeking behavior. CONCLUSION: These results suggest the utility of an SSFO-based approach for enhancing activity in a structure without driving specific patterns of neuronal firing. However, the utility of an SSFO-based approach for axon terminal stimulation remains unclear. Moreover, these results suggest that the ability of the IL to reduce cocaine seeking depends, at least in part, on rats first having undergone extinction training.
RATIONALE: The infralimbic cortex (IL) and its downstream projection target the nucleus accumbens shell (NAshell) mediate the active suppression of cocaine-seeking behavior. Although an optogenetic approach would be beneficial for stimulating the IL and its efferents to study their role during reinstatement of cocaine seeking, the use of channelrhodopsin introduces significant difficulties, as optimal stimulation parameters are not known. OBJECTIVES: The present experiments utilized a stable step-function opsin (SSFO) to potentiate endogenous activity in the IL and in IL terminals in the NAshell during cocaine-seeking tests to determine how these manipulations affect cocaine-seeking behaviors. METHODS:Rats first underwent 6-h access cocaine self-administration followed by 21-27 days in the homecage. Rats then underwent cue-induced and cocaine-primed drug-seeking tests during which the optogenetic manipulation was given. The same rats then underwent extinction training, followed by cue-induced and cocaine-primed reinstatements. RESULTS: Potentiation of endogenous IL activity did not significantly alter cue-induced or cocaine-primed drug seeking following the homecage period. However, following extinction training, enhancement of endogenous IL activity attenuated cue-induced reinstatement by 35% and cocaine-primed reinstatement by 53%. Stimulation of IL terminals in the NAshell did not consistently alter cocaine-seeking behavior. CONCLUSION: These results suggest the utility of an SSFO-based approach for enhancing activity in a structure without driving specific patterns of neuronal firing. However, the utility of an SSFO-based approach for axon terminal stimulation remains unclear. Moreover, these results suggest that the ability of the IL to reduce cocaine seeking depends, at least in part, on rats first having undergone extinction training.
Entities:
Keywords:
Channelrhodopsin; Cocaine seeking; Incubation of craving; Optogenetics; Reinstatement
Authors: Angela M Kearns; Benjamin M Siemsen; Jordan L Hopkins; Rachel A Weber; Michael D Scofield; Jamie Peters; Carmela M Reichel Journal: Addict Biol Date: 2021-08-25 Impact factor: 4.280
Authors: Victória A Müller Ewald; Jangjin Kim; Sean J Farley; John H Freeman; Ryan T LaLumiere Journal: Addict Biol Date: 2021-10-20 Impact factor: 4.093
Authors: Alvin S Chiu; Matthew C Kang; Laura L Huerta Sanchez; Anne M Fabella; Kalysta N Holder; Brooke D Barger; Kristina N Elias; Christina B Shin; C Leonardo Jimenez Chavez; Tod E Kippin; Karen K Szumlinski Journal: Neuropsychopharmacology Date: 2021-06-29 Impact factor: 7.853