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Saint-André-lez-Lille, France

De Guglielmo G.,University of Camerino | Cippitelli A.,University of Camerino | Somaini L.,Addiction Treatment Center | Gerra G.,Drug Prevention and Health Branch | And 5 more authors.
Addiction Biology | Year: 2013

Pregabalin (Lyrica™) is a structural analog of γ-aminobutyric acid (GABA) and is approved by the FDA for partial epilepsy, neuropathic pain and generalized anxiety disorders. Pregabalin also reduces excitatory neurotransmitter release and post-synaptic excitability. Recently, we demonstrated that pregabalin reduced alcohol intake and prevented relapse to the alcohol seeking elicited by stress or environmental stimuli associated with alcohol availability. Here, we sought to extend these findings by examining the effect of pregabalin on cocaine self-administration (0.25 mg/infusion) and on cocaine seeking elicited by both conditioned stimuli and stress, as generated by administration of yohimbine (1.25 mg/kg). The results showed that oral administration of pregabalin (0, 10 or 30 mg/kg) reduced self-administration of cocaine over an extended period (6 hours), whereas it did not modify self-administration of food. In cocaine reinstatement studies, pregabalin (10 and 30 mg/kg) abolished the cocaine seeking elicited by both the pharmacological stressor yohimbine and the cues predictive of cocaine availability. Overall, these results demonstrate that pregabalin may have potential in the treatment of some aspects of cocaine addiction. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction. Source


Moretti S.,University of Milan | Castelli M.,University of Milan | Franchi S.,University of Milan | Raggi M.A.,University of Bologna | And 5 more authors.
Journal of Leukocyte Biology | Year: 2014

Marijuana abuse is prominent among adolescents. Although Δ9-THC, one of its main components, has been demonstrated to modulate immunity in adults, little is known about its impact during adolescence on the immune system and the long-lasting effects in adulthood. We demonstrate that 10 days of Δ9-THC treatment induced a similar alteration of macrophage and splenocyte cytokines in adolescent and adult mice. Immediately at the end of chronic Δ9-THC, a decrease of proinflammatory cytokines IL- 1β and TNF-α and an increase of anti-inflammatory cytokine IL-10 production by macrophages were present as protein and mRNA in adolescent and adult mice. In splenocytes, Δ9-THC modulated Th1/Th2 cytokines skewing toward Th2: IFN-γ was reduced, and IL-4 and IL-10 increased. These effects were lost in adult animals, 47 days after the last administration. In contrast, in adult animals treated as adolescents, a perturbation of immune responses, although in an opposite direction, was present. In adults treated as adolescents, a proinflammatory macrophage phenotype was observed (IL-1β and TNF-α were elevated; IL-10 decreased), and the production of Th cytokines was blunted. IgM titers were also reduced. Corticosterone concentrations indicate a long-lasting dysregulation of HPA in adolescent mice. We measured blood concentrations of Δ9-THC and its metabolites, showing that Δ9-THC plasma levels in our mice are in the order of those achieved in human heavy smokers. Our data demonstrate that Δ9-THC in adolescent mice triggers immune dysfunctions that last long after the end of abuse, switching the murine immune system to proinflammatory status in adulthood. © Society for Leukocyte Biology. Source


Saracino M.A.,University of Bologna | Gerra G.,United Nations Office on Drugs and Crime | Somaini L.,Addiction Treatment Center | Colombati M.,University of Bologna | Raggi M.A.,University of Bologna
Journal of Chromatography A | Year: 2010

An isocratic high-performance liquid chromatographic method has been developed for the measurement of serotonin, 5-hydroxyindolacetic and homovanillic acids in dried blood spots and in platelet poor and rich plasma samples. Analyses were carried out on a C18 reversed-phase column using a mobile phase composed of 13% methanol and 87% aqueous citrate buffer, containing octanesulfonic and ethylendiaminotetracetic acids. Coulometric detection was used, setting the guard cell at +0.100V, the first analytical cell at -0.200V and the second analytical cell at +0.400V. For the pre-treatment of biological samples a novel solid-phase extraction procedure, based on mixed-mode reversed-phase - strong anion exchange Oasis cartridges, was implemented. Extraction yields of the analytes from all these matrices were satisfactory, being always higher than 89.0%. The calibration curve was linear over the on-column concentration range of 0.1-22.5ngmL-1 for serotonin and 5-hydroxyindolacetic acid and of 0.25-22.5ngmL-1 for homovanillic acid. The sensitivity was good with a limit of detection of 0.05ngmL-1 for serotonin and 5-hydroxyindolacetic acid and 0.12ngmL-1 for homovanillic acid. Results were also satisfactory in terms of precision, selectivity and accuracy. The analytical method was successfully applied to human platelet poor and rich plasma samples and to dried blood spots from volunteers and psychiatric patients. © 2010. Source


Saracino M.A.,University of Bologna | Iacono C.,University of Bologna | Somaini L.,Addiction Treatment Center | Gerra G.,Drug Prevention and Health Branch | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

The development and validation of a bioanalytical assay for the simultaneous determination of cortisol, cortisone and corticosterone levels in several matrices, such as saliva, plasma, blood and urine samples have been described. The method is based on a rapid test which combines a microextraction by packed sorbent procedure and liquid chromatography-diode array technique. Chromatographic separation of the analytes (cortisol, cortisone and corticosterone) and the internal standard (methylprednisolone) was achieved in less than 10min on a reversed-phase pentafluorophenyl column using a mobile phase composed of phosphate buffer and acetonitrile. The assay was performed after an innovative microextraction procedure by means of C8 sorbent which guaranteed good clean-up of the matrices and satisfactory extraction yield of the analytes. Moreover, the method gave linear results over a range of 5-100ngmL-1 and showed good selectivity and precision.This method was successfully applied for quantifying corticosteroids in specific matrices derived from some healthy volunteers in comparison to two socially diversified groups, namely former heroin addicts undergoing opioid replacement therapy and poly-drug abusers. © 2013 Elsevier B.V. Source


Mercolini L.,University of Bologna | Mandrioli R.,Ministry for International Cooperation and Integration | Sorella V.,University of Bologna | Somaini L.,Corso dAugusto | And 3 more authors.
Journal of Chromatography A | Year: 2013

A sensitive and selective HPLC-MS/MS method has been developed for the first time for the analysis of Δ9-tetrahydrocannabinol (the most important active cannabinoid) and its hydroxylated and carboxylated metabolites in human Dried Blood Spots (DBSs). The simultaneous determination of Δ9-tetrahydrocannabinol and its two main metabolites allows assessing the time elapsed after the drug intake and distinguishing between acute or former consumption. This is an important information in specific contexts such as " on street" controls by police forces. DBSs have been chosen as the optimal biological matrix for this kind of testing, since they provide information on the actual state of intoxication, without storage and transportation problems usually associated with classical blood testing. The analysis is carried out on a C8 reversed phase column with a mobile phase composed of 0.1% formic acid in a water/methanol mixture and an electrospray ionisation (ESI) source, coupled to a triple quadrupole mass spectrometer. The method was validated according to international guidelines, with satisfactory results in terms of extraction yields, precision, stability and accuracy. Application to real DBS samples from Cannabis abusers gave reliable results, thus confirming the methodology suitability for roadside testing. © 2012 Elsevier B.V. Source

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