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Frequency of cocaine self-administration influences drug seeking in the rat: optogenetic evidence for a role of the prelimbic cortex.
Neuropsychopharmacology 2014; 39(10):2317-30N

Abstract

High-frequency intake and high drug-induced seeking are associated with cocaine addiction in both human and animals. However, their relationships and neurobiological underpinnings remain hypothetical. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and nucleus accumbens (NAc) have been shown to have a role in cocaine seeking. However, their involvement in regulating high-frequency intake and high cocaine-induced seeking is unclear. We manipulated frequency of cocaine self-administration and investigated whether it influenced cocaine seeking. The contribution of the aforementioned structures was evaluated using changes in expression of the immediate early gene c-Fos and targeted optogenetic manipulations. Rats that self-administered at High frequency (short inter-infusion intervals allowed by short time-out) showed higher cocaine-induced seeking than low frequency rats (long inter-infusions intervals imposed by long time-out), as measured with cocaine-induced reinstatement. c-Fos was enhanced in High frequency rats in the prelimbic (PL) and infralimbic (IL) areas of the mPFC, the BLA, and the NAc core and shell. Correlational analysis of c-Fos revealed that the PL was a critical node strongly correlated with both the IL and NAc core in High frequency rats. Targeted optogenetic inactivation of the PL decreased cocaine-induced reinstatement, but increased cocaine self-administration, in High frequency rats. In contrast, optogenetic activation of the PL had no effect on Low frequency rats. Thus, high-frequency intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory or inhibitory effect, depending on operant contingencies. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake.

Authors+Show Affiliations

1] INSERM U862, Pathophysiology of Addiction, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France [2] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France [3] Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, C/ Dr Aiguader 88, Barcelona, Spain.1] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France [2] INSERM U862, Neuronal Circuits of Associative Learning, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France.1] INSERM U862, Pathophysiology of Addiction, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France [2] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France.1] INSERM U862, Pathophysiology of Addiction, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France [2] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France.1] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France [2] INSERM U862, Neuronal Circuits of Associative Learning, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France.1] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France [2] INSERM U862, Neuronal Circuits of Associative Learning, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France.1] University of Bordeaux, Bordeaux Imaging Center, Bordeaux, France [2] CNRS, Bordeaux Imaging Center, Bordeaux, France [3] INSERM, Bordeaux Imaging Center, Bordeaux, France.1] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France [2] INSERM U862, Neuronal Circuits of Associative Learning, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France.1] INSERM U862, Pathophysiology of Addiction, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux, Cedex, France [2] University of Bordeaux, 146 Rue Léo Saignat, Bordeaux, Cedex, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24633559

Citation

Martín-García, Elena, et al. "Frequency of Cocaine Self-administration Influences Drug Seeking in the Rat: Optogenetic Evidence for a Role of the Prelimbic Cortex." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 39, no. 10, 2014, pp. 2317-30.
Martín-García E, Courtin J, Renault P, et al. Frequency of cocaine self-administration influences drug seeking in the rat: optogenetic evidence for a role of the prelimbic cortex. Neuropsychopharmacology. 2014;39(10):2317-30.
Martín-García, E., Courtin, J., Renault, P., Fiancette, J. F., Wurtz, H., Simonnet, A., ... Deroche-Gamonet, V. (2014). Frequency of cocaine self-administration influences drug seeking in the rat: optogenetic evidence for a role of the prelimbic cortex. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 39(10), pp. 2317-30. doi:10.1038/npp.2014.66.
Martín-García E, et al. Frequency of Cocaine Self-administration Influences Drug Seeking in the Rat: Optogenetic Evidence for a Role of the Prelimbic Cortex. Neuropsychopharmacology. 2014;39(10):2317-30. PubMed PMID: 24633559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Frequency of cocaine self-administration influences drug seeking in the rat: optogenetic evidence for a role of the prelimbic cortex. AU - Martín-García,Elena, AU - Courtin,Julien, AU - Renault,Prisca, AU - Fiancette,Jean-François, AU - Wurtz,Hélène, AU - Simonnet,Amélie, AU - Levet,Florian, AU - Herry,Cyril, AU - Deroche-Gamonet,Véronique, Y1 - 2014/03/17/ PY - 2013/12/06/received PY - 2014/03/09/revised PY - 2014/03/09/accepted PY - 2014/3/18/entrez PY - 2014/3/19/pubmed PY - 2015/4/16/medline SP - 2317 EP - 30 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 39 IS - 10 N2 - High-frequency intake and high drug-induced seeking are associated with cocaine addiction in both human and animals. However, their relationships and neurobiological underpinnings remain hypothetical. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and nucleus accumbens (NAc) have been shown to have a role in cocaine seeking. However, their involvement in regulating high-frequency intake and high cocaine-induced seeking is unclear. We manipulated frequency of cocaine self-administration and investigated whether it influenced cocaine seeking. The contribution of the aforementioned structures was evaluated using changes in expression of the immediate early gene c-Fos and targeted optogenetic manipulations. Rats that self-administered at High frequency (short inter-infusion intervals allowed by short time-out) showed higher cocaine-induced seeking than low frequency rats (long inter-infusions intervals imposed by long time-out), as measured with cocaine-induced reinstatement. c-Fos was enhanced in High frequency rats in the prelimbic (PL) and infralimbic (IL) areas of the mPFC, the BLA, and the NAc core and shell. Correlational analysis of c-Fos revealed that the PL was a critical node strongly correlated with both the IL and NAc core in High frequency rats. Targeted optogenetic inactivation of the PL decreased cocaine-induced reinstatement, but increased cocaine self-administration, in High frequency rats. In contrast, optogenetic activation of the PL had no effect on Low frequency rats. Thus, high-frequency intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory or inhibitory effect, depending on operant contingencies. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/24633559/Frequency_of_cocaine_self_administration_influences_drug_seeking_in_the_rat:_optogenetic_evidence_for_a_role_of_the_prelimbic_cortex_ L2 - http://dx.doi.org/10.1038/npp.2014.66 DB - PRIME DP - Unbound Medicine ER -