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Involvement of the lateral orbitofrontal cortex in drug context-induced reinstatement of cocaine-seeking behavior in rats.
Eur J Neurosci. 2009 Oct; 30(7):1370-81.EJ

Abstract

Orbitofrontal cortex (OFC) damage produces impaired decision-making, impulsivity and perseveration and potentially contributes to compulsive drug seeking in cocaine users. To further explore this phenomenon, we assessed the role of the lateral OFC (lOFC) in drug context-induced cocaine-seeking behavior in the reinstatement model of drug relapse. Rats were trained to lever press for intravenous cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a different context (extinction-paired context). Reinstatement of cocaine seeking (non-reinforced lever presses) was assessed in the cocaine context in the absence of response-contingent stimuli. In Experiment 1, we evaluated whether acute inhibition of lOFC output alters context-induced cocaine-seeking behavior by infusing the GABA(B + A) agonists (baclofen + muscimol) or vehicle into the lOFC immediately before exposure to the cocaine-paired context. In Experiments 2 and 3, we assessed how prolonged loss of lOFC output affects drug context-induced cocaine seeking by administering bilateral N-methyl-d-aspartic acid or sham lesions of the lOFC either before or after self-administration and extinction training. Remarkably, IOFC functional inactivation attenuated, post-training lesions failed to alter and pre-training lesions potentiated drug context-induced cocaine seeking without altering responding in the extinction context. These results suggest that neural activity in the lOFC promotes context-induced cocaine-seeking behavior. However, prolonged loss of lOFC output enhances the motivational salience of cocaine-paired contextual stimuli probably by eliciting compensatory neuroadaptations, with the effects of post-training lOFC lesions reflecting an intermediate state of compensatory neuroplasticity. Overall, these findings support the idea that OFC dysfunction may promote cue reactivity and enhance relapse propensity in cocaine users.

Authors+Show Affiliations

Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19769591

Citation

Lasseter, Heather C., et al. "Involvement of the Lateral Orbitofrontal Cortex in Drug Context-induced Reinstatement of Cocaine-seeking Behavior in Rats." The European Journal of Neuroscience, vol. 30, no. 7, 2009, pp. 1370-81.
Lasseter HC, Ramirez DR, Xie X, et al. Involvement of the lateral orbitofrontal cortex in drug context-induced reinstatement of cocaine-seeking behavior in rats. Eur J Neurosci. 2009;30(7):1370-81.
Lasseter, H. C., Ramirez, D. R., Xie, X., & Fuchs, R. A. (2009). Involvement of the lateral orbitofrontal cortex in drug context-induced reinstatement of cocaine-seeking behavior in rats. The European Journal of Neuroscience, 30(7), 1370-81. https://doi.org/10.1111/j.1460-9568.2009.06906.x
Lasseter HC, et al. Involvement of the Lateral Orbitofrontal Cortex in Drug Context-induced Reinstatement of Cocaine-seeking Behavior in Rats. Eur J Neurosci. 2009;30(7):1370-81. PubMed PMID: 19769591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of the lateral orbitofrontal cortex in drug context-induced reinstatement of cocaine-seeking behavior in rats. AU - Lasseter,Heather C, AU - Ramirez,Donna R, AU - Xie,Xiaohu, AU - Fuchs,Rita A, Y1 - 2009/09/21/ PY - 2009/9/23/entrez PY - 2009/9/23/pubmed PY - 2010/1/19/medline SP - 1370 EP - 81 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 30 IS - 7 N2 - Orbitofrontal cortex (OFC) damage produces impaired decision-making, impulsivity and perseveration and potentially contributes to compulsive drug seeking in cocaine users. To further explore this phenomenon, we assessed the role of the lateral OFC (lOFC) in drug context-induced cocaine-seeking behavior in the reinstatement model of drug relapse. Rats were trained to lever press for intravenous cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a different context (extinction-paired context). Reinstatement of cocaine seeking (non-reinforced lever presses) was assessed in the cocaine context in the absence of response-contingent stimuli. In Experiment 1, we evaluated whether acute inhibition of lOFC output alters context-induced cocaine-seeking behavior by infusing the GABA(B + A) agonists (baclofen + muscimol) or vehicle into the lOFC immediately before exposure to the cocaine-paired context. In Experiments 2 and 3, we assessed how prolonged loss of lOFC output affects drug context-induced cocaine seeking by administering bilateral N-methyl-d-aspartic acid or sham lesions of the lOFC either before or after self-administration and extinction training. Remarkably, IOFC functional inactivation attenuated, post-training lesions failed to alter and pre-training lesions potentiated drug context-induced cocaine seeking without altering responding in the extinction context. These results suggest that neural activity in the lOFC promotes context-induced cocaine-seeking behavior. However, prolonged loss of lOFC output enhances the motivational salience of cocaine-paired contextual stimuli probably by eliciting compensatory neuroadaptations, with the effects of post-training lOFC lesions reflecting an intermediate state of compensatory neuroplasticity. Overall, these findings support the idea that OFC dysfunction may promote cue reactivity and enhance relapse propensity in cocaine users. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/19769591/Involvement_of_the_lateral_orbitofrontal_cortex_in_drug_context_induced_reinstatement_of_cocaine_seeking_behavior_in_rats_ L2 - https://doi.org/10.1111/j.1460-9568.2009.06906.x DB - PRIME DP - Unbound Medicine ER -