Skip to main content
Log in

Attenuation of cocaine seeking in rats via enhancement of infralimbic cortical activity using stable step-function opsins

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science (New York, NY) 282:298–300

    Article  CAS  Google Scholar 

  • Augur IF, Wyckoff AR, Aston-Jones G, Kalivas PW, Peters J (2016) Chemogenetic activation of an extinction neural circuit reduces cue-induced reinstatement of cocaine seeking. J Neurosci 36:10174–10180

    Article  CAS  Google Scholar 

  • Beshel J, Kopell N, Kay LM (2007) Olfactory bulb gamma oscillations are enhanced with task demands. J Neurosci 27:8358–8365

    Article  CAS  Google Scholar 

  • Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114

    Article  Google Scholar 

  • Donnelly NA, Holtzman T, Rich PD, Nevado-Holgado AJ, Fernando AB, Van Dijck G, Holzhammer T, Paul O, Ruther P, Paulsen O, Robbins TW, Dalley JW (2014) Oscillatory activity in the medial prefrontal cortex and nucleus accumbens correlates with impulsivity and reward outcome. PLoS One 9:e111300

    Article  Google Scholar 

  • Fries P, Nikolic D, Singer W (2007) The gamma cycle. Trends Neurosci 30:309–316

    Article  CAS  Google Scholar 

  • Fries P, Reynolds JH, Rorie AE, Desimone R (2001) Modulation of oscillatory neuronal synchronization by selective visual attention. Science (New York, NY) 291:1560–1563

    Article  CAS  Google Scholar 

  • Gorelova N, Yang CR (1997) The course of neural projection from the prefrontal cortex to the nucleus accumbens in the rat. Neuroscience 76:689–706

    Article  CAS  Google Scholar 

  • Gutman AL, Nett KE, Cosme CV, Worth WR, Gupta SC, Wemmie JA, LaLumiere RT (2017) Extinction of cocaine seeking requires a window of infralimbic pyramidal neuron activity after unreinforced lever presses. J Neurosci 37:6075–6086

    Article  CAS  Google Scholar 

  • Huff ML, Emmons EB, Narayanan NS, LaLumiere RT (2016) Basolateral amygdala projections to ventral hippocampus modulate the consolidation of footshock, but not contextual, learning in rats. Learn Mem (Cold Spring Harbor, NY) 23: 51–60

  • Huff ML, Miller RL, Deisseroth K, Moorman DE, LaLumiere RT (2013) Posttraining optogenetic manipulations of basolateral amygdala activity modulate consolidation of inhibitory avoidance memory in rats. Proc Natl Acad Sci U S A 110:3597–3602

    Article  CAS  Google Scholar 

  • Kelley AE (2004) Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci Biobehav Rev 27:765–776

    Article  Google Scholar 

  • LaLumiere RT, Niehoff KE, Kalivas PW (2010) The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration. Learn Mem (Cold Spring Harbor, NY) 17:168–175

    Article  CAS  Google Scholar 

  • LaLumiere RT, Smith KC, Kalivas PW (2012) Neural circuit competition in cocaine-seeking: roles of the infralimbic cortex and nucleus accumbens shell. Eur J Neurosci 35:614–622

    Article  Google Scholar 

  • Lenoir M, Guillem K, Koob GF, Ahmed SH (2012) Drug specificity in extended access cocaine and heroin self-administration. Addict Biol 17:964–976

    Article  CAS  Google Scholar 

  • Liu Z, Wang Y, Cai L, Li Y, Chen B, Dong Y, Huang YH (2016) Prefrontal cortex to accumbens projections in sleep regulation of reward. J Neurosci 36:7897–7910

    Article  CAS  Google Scholar 

  • Ma YY, Lee BR, Wang X, Guo C, Liu L, Cui R, Lan Y, Balcita-Pedicino JJ, Wolf ME, Sesack SR, Shaham Y, Schluter OM, Huang YH, Dong Y (2014) Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections. Neuron 83:1453–1467

    Article  CAS  Google Scholar 

  • Muller Ewald VA, LaLumiere RT (2017) Neural systems mediating the inhibition of cocaine-seeking behaviors. Pharmacol Biochem Behav

  • Pesaran B, Pezaris JS, Sahani M, Mitra PP, Andersen RA (2002) Temporal structure in neuronal activity during working memory in macaque parietal cortex. Nat Neurosci 5:805–811

    Article  CAS  Google Scholar 

  • Peters J, Kalivas PW, Quirk GJ (2009) Extinction circuits for fear and addiction overlap in prefrontal cortex. Learn Mem (Cold Spring Harbor, NY) 16: 279–288

  • Peters J, LaLumiere RT, Kalivas PW (2008) Infralimbic prefrontal cortex is responsible for inhibiting cocaine seeking in extinguished rats. J Neurosci 28:6046–6053

    Article  CAS  Google Scholar 

  • Pickens CL, Airavaara M, Theberge F, Fanous S, Hope BT, Shaham Y (2011) Neurobiology of the incubation of drug craving. Trends Neurosci 34:411–420

    Article  CAS  Google Scholar 

  • Tallon-Baudry C, Kreiter A, Bertrand O (1999) Sustained and transient oscillatory responses in the gamma and beta bands in a visual short-term memory task in humans. Vis Neurosci 16:449–459

    Article  CAS  Google Scholar 

  • Van den Oever MC, Rotaru DC, Heinsbroek JA, Gouwenberg Y, Deisseroth K, Stuber GD, Mansvelder HD, Smit AB (2013) Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory. J Neurosci 33:18225–18233

    Article  Google Scholar 

  • Yizhar O, Fenno LE, Davidson TJ, Mogri M, Deisseroth K (2011a) Optogenetics in neural systems. Neuron 71:9–34

    Article  CAS  Google Scholar 

  • Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011b) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178

    Article  CAS  Google Scholar 

Download references

Funding

R.T.L was supported by National Institute of Health R01 DA034684. J.A.W. was supported by the Department of Veterans Affairs (Merit Award), National Institute on Drug Abuse R01 DA037216, National Heart, Lung and Blood Institute R01 HL113863, and the Carver Foundation. N.S.N. was supported by National Institute of Health R01 NS089470.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Victória A. Müller Ewald.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

This article belongs to a Special Issue on Psychopharmacology of Extinction.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Müller Ewald, V.A., De Corte, B.J., Gupta, S.C. et al. Attenuation of cocaine seeking in rats via enhancement of infralimbic cortical activity using stable step-function opsins. Psychopharmacology 236, 479–490 (2019). https://doi.org/10.1007/s00213-018-4964-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-018-4964-y

Keywords

Navigation