Different Psychological States Sustain Drug-Induced Reactivation of Cocaine Conditioned Place Preference in the Mouse

Tangui Maurice1, 2, 3, 4, *, Julie Espallergues1, 2, 3, 4, Charleine Zussy1, 2, 3, 4, Johann Meunier1, 2, 3, 4, Clémence Borys3, 4, Elodie George 3, 4, Pascal Romieu 3, 4, 5
1 INSERM U 710, 34095 Montpellier, France
2 EPHE, 75017 Paris, France
3 University of Montpellier II, 34095 Montpellier, France
4 CNRS FRE 2693, 34095 Montpellier, France
5 INSERM U 575, 67084 Strasbourg, France

© 2008 Maurice et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the INSERM U. 710, University of Montpellier II, cc 105, pl. E. Bataillon, 34095 Montpellier cedex 5, France; Tel: +33/0 4 67 14 36 23; Fax: +33/0 4 67 14 33 86; E-mail:


Cocaine-seeking behavior can be investigated in rodents using the conditioned place preference (CPP) paradigm. CPP can be extinguished and then reactivated using cocaine priming. To study the role of dopaminergic receptors in CPP reinstatement, CPP was induced in Swiss mice using cocaine (30 mg/kg ip) and extinguished with saline. CPP reactivation was examined by treatment with the D1 receptor antagonist SCH23,390 (0.03-1 mg/kg), the D2 antagonist raclopride (0.1-3 mg/kg) or the D3 antagonist U-99,194A (20-40 mg/kg), alone or before cocaine (15 mg/kg). Cocaine priming reactivated CPP up to 220% of the post-conditioning response. SCH23,390 and raclopride induced, alone at 0.3 mg/kg, reactivation of cocaine-induced CPP, but only SCH23,390 blocked the cocaine-induced reactivation. U99,194A failed to promote CPP reactivation alone or to affect the cocaine response. CPP reactivation involving contextual learning could be induced using a single-reconditioning session after extinction. Treatment with cocaine or raclopride, but not SCH23,390, induced CPP reactivation. Finally, the emotional state of mice was tested during reactivation under drug treatments in the elevated maze procedure and an anxiety state was measured after 0.3 mg/kg SCH23,390. These observations showed that in cocaine-conditioned animals and then extinguished, blockade of D1 receptors induces an anxiogeniclike state, able to promote a cocaine-sensitive CPP reactivation. Blockade of D2 receptor promoted a cocaine-mimetic CPP reactivation. Therefore, two different psychological states underlie CPP reactivation by drug priming: a 'drug craving CPP' induced by dopamine systems-mediated anxiety and a 'drug retrieval CPP' promoted by incentive learning processes.