Search

Derivatives from the Cannabis plant are the most commonly abused illegal substances in the world. The main psychoactive component found in the plant, Δ-9-tetrahydrocannabinol (THC), exerts its effects through the endocannabinoid system. Manipulations of this system affect some types of learning that seem to be dependent on dorsal striatum synaptic plasticity. Dendritic spines exhibit important synaptic functional attributes and a potential for plasticity, which is thought to mediate long-lasting changes in behaviour. To study the possible structural plasticity changes that prolonged THC administration might exert in the dorsal striatum, adult, male C57BL6/J mice were intraperitoneally injected with THC (10mg/kg) or vehicle for 15 days followed by a 7-day drug-free period. Using single cell intracellular injections of Lucifer Yellow, confocal microscopy, and 3D reconstruction of labelled neurons, we studied dendritic spine density and spine size in medium spiny neurons (MSNs) of the anterior dorsolateral striatum (aDLS) and posterior dorsomedial striatum (pDMS). We found that the THC treatment increased dendritic spine density in the distal part of the dendrites of MSNs in the pDMS, but no changes were found in the rest of the parameters analysed in either region studied. We also observed that dendritic spines of MSNs of pDMS presented lower volume and surface area values than MSNs of the aDLS. These results seem to indicate that THC could induce structural plasticity alterations in the circuits involving pDMS MSNs. [ABSTRACT FROM AUTHOR]

Dose–response studies are thought to be a valuable tool to predict the most genetically drug-vulnerable individuals. However, dose–response curves for morphine self-administration have not yet been examined and nor strain differences might be evident. Therefore, this study aimed to define the dose–response curve for morphine self-administration (0.25, 0.5, 1 and 2 mg/kg) in Lewis (LEW) rats and their histocompatible Fischer-344 (F344) rats. In addition, impulsivity has been suggested as one of the genetic factors contributing most to the initiation of drug use. Therefore, the impulsive choice of both rat strains in the presence or absence of the same morphine doses was also analysed. LEW rats self-administered significantly more morphine whatever the dose tested and they exhibited greater basal impulsive choice compared with F344 rats. The F344 strain showed a preference for the dose of 0.5 mg/kg, while any of the doses used had a differential reinforcing effect in the LEW strain. The basal pattern of strain differences in impulsive choice was not affected by morphine administration. These data suggest that the LEW strain has a highly drug-vulnerable phenotype and they point to the strength of impulsivity as a pre-existing behavioural trait that might make this rat strain more vulnerable to the reinforcing effects of drugs and, therefore, to develop addiction. [ABSTRACT FROM PUBLISHER]

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.Neuropsychopharmacology (2008) 33, 806–813; doi:10.1038/sj.npp.1301467; published online 6 June 2007 [ABSTRACT FROM AUTHOR]