One aspect of the addictive process that has not been thoroughly investigated is the consequence of the frustrated state occurring when the drug is not available. The present study aimed to validate a novel operant model of frustrated expected reward in mice. C57BL/6J mice were trained in operant conditioning maintained by chocolate-flavoured pellets or cocaine. After the completion of high rates of responding on a progressive ratio schedule, the reward was unexpectedly withheld. The consequences of this frustrated behaviour on anxiety, aggressiveness, perseveration, extinction and reinstatement were investigated. Mice exposed to the frustrated event perseverated in the operant responses and showed increased aggressiveness in the resident-intruder test. These animals also showed higher rates of cue-induced reinstatement of drug seeking. The present study provides a reliable operant model in mice to evaluate a frustrated state following reward unavailability. This animal model could be useful to study the behavioural and neurochemical consequences related to the emotional states generated during the omission of a highly expected reward.

This work was supported by the DG Research of the European Commission (PHECOMP, no. LHSM-CT-2007—037669 and GENADDICT, no. LSHM-CT-2004—05166), the Spanish ‘Instituto de Salud Carlos III’ (RTA, no. RD06/001/001), the Spanish ‘Ministerio de Ciencia e Innovación’ (no. SAF2007-64062), the Spanish ‘Ministerio de Sanidad, Política Social e Igualdad’ (Plan/nNacional Sobre Drogas, no. 2009/026), the Catalan Government (SGR2009-00131), the ICREA Foundation (ICREA Academia-2008). A.B. was supported by an FI pre-doctoral fellowship of the Catalan Government; J.G.-C. was supported by a ‘Juan de la Cierva’ postdoctoral fellowship from the Spanish ‘Ministerio de Ciencia e Innovación’; and E.M.-G. was supported by a ‘Sara Borrell’ post-doctoral fellowship from the Spanish ‘Instituto de Salud Carlos III’. Partial support from FEDER funds is also acknowledged