Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates

A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitarygonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that methadone dosages were not significantly correlated with sexual dysfunction scores except for 'erectile dysfunction', for which an inverse association was evidenced. Testosterone values showed a significant inverse correlation with ASEX sexual dysfunction scores, CECA-Q neglect scores and psychiatric symptom at SCL 90 among methadone patients. PRL levels were directly and significantly correlated with sexual dysfunction scores, psychiatric symptoms at SCL 90 and CECA-Q neglect scores. Both testosterone and PRL did not correlate with methadone dosages. The present findings appear to support the view of childhood adversities and comorbid psychiatric symptoms contributing to sexual dysfunction and related hormonal changes among methadone patients, challenging the assumption that attributes sexual problems entirely to the direct pharmacological effects of opioid agonist medications

Pregabalin reduces cocaine self-administration and relapse to cocaine seeking in the rat

Pregabalin (Lyrica™) is a structural analog of g-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

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Nuova edizione italian

Functional interaction between different receptor systems in the modulation of neurotransmitter release from the guinea-pig myenteric plexus.

SIENA-CERTOSA DI PONTIGNAN

Fast analysis of catecholamine metabolites MHPG and VMA in human plasma by HPLC with fluorescence detection and a novel SPE procedure

A fast and sensitive high-performance liquid chromatographic method has been developed for the determination in human plasma of MHPG (3-methoxy-4-hydroxyphenylethylenglycol) and VMA (vanillyl mandelic acid), the main metabolites of epinephrine and norepinephrine. Analyses were carried out at 325 nm while exciting at 285 nm on a reversed-phase column (Atlantis C18, 150 74.6 mm I.D., 5 \u3bcm) using a mobile phase composed of 2% methanol and 98% aqueous citrate buffer at pH 3.0. A careful solid-phase extraction procedure, based on mixed-mode reversed phase - strong anion exchange Oasis cartridges (MAX, 30 mg, 1 mL), was developed for the pre-treatment of plasma samples. Extraction yields were satisfactory, always higher than 90%. Calibration curves were linear over the 0.2-40.0 ng/mL concentration range for MHPG and over the 0.5-40.0 ng/mL concentration range for VMA. The method was successfully applied to plasma samples of former drug users undergoing detoxification therapy and subjects \u201cat risk\u201d of developing drug addiction

Chromatographic analysis of serotonin, 5-hydroxyindolacetic acid and homovanillic acid in dried blood spots and platelet poor and rich plasma samples

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 +0.100 V, the first analytical cell at −0.200 V and the second analytical cell at +0.400 V. For the pre-treatment of biological samples a novel solid-phase extraction procedure, based on mixed-mode reversed-phase \u2013 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\u201322.5 ng mL−1 for serotonin and 5-hydroxyindolacetic acid and of 0.25\u201322.5 ng mL−1 for homovanillic acid. The sensitivity was good with a limit of detection of 0.05 ng mL−1 for serotonin and 5-hydroxyindolacetic acid and 0.12 ng mL−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