1. ¹Departamento de Psicobiología, Facultad de Psicología, Universidad Nacional de Educacion a Distancia, Madrid, Spain
2. ²Laboratorio de Imagen Médica, Unidad de Medicina y Cirugía Experimental, Hospital General Gregorio Marañon, Madrid, Spain

Correspondence: Emilio Ambrosio, Departamento de Psicobiología, Facultad de Psicología, Universidad Nacional de Educación a Distancia, C/Juan del Rosal n°10, 28040 Madrid, Spain. Tel: +34 913 987 974; Fax: +34 913 986 287; E-mail: eambrosio@psi.uned.es

Received 17 November 2006; Revised 2 May 2007; Accepted 3 May 2007; Published online 6 June 2007.

Abstract

Marijuana consumption during adolescence has been proposed to be a stepping-stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self-administration (1 mg/kg), food-reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food-restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [¹⁸F]-fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP-treated rats showed a higher rate of cocaine self-administration as compared to vehicle-treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food-reinforced operant task, pointing to the cocaine-specific nature of the effect seen in self-administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP-treated females when compared to their vehicle-treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo-entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self-administration, in a sex-specific fashion. This increased susceptibility could be related to the changes in brain metabolic activity induced by cannabinoids during adolescence.