title: Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence.
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 [(18)F]-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.
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, Universidad Nacional de Educacion a Distancia, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Higuera-Matas
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Soto-Montenegro
authors.forename: Nuria
authors.initials: N
authors.lastname: del Olmo
authors.forename: Miguel
authors.initials: M
authors.lastname: Miguéns
authors.forename: Isabel
authors.initials: I
authors.lastname: Torres
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Vaquero
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Lecumberri
authors.forename: Manuel
authors.initials: M
authors.lastname: Desco
authors.forename: Emilio
authors.initials: E
authors.lastname: Ambrosio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D012737:Sex Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D019788:Fluorodeoxyglucose F18; D003042:Cocaine; D005947:Glucose