No abstract

Variants of the opioid receptors are the obvious candidates underlying addiction. The kappa opioid receptor (KOR) system seems to play a role in stress responsivity, opiate withdrawal and responses to psycho-stimulants, inhibiting mesolimbic dopamine. KOR gene polymorphisms have been reported to contribute to predisposition to voluntary alcohol-drinking behavior in experimental animals. In humans, the 36G > T single nucleotide polymorphism (SNP) on KOR gene, that was recently identified, has been found associate with substance dependence, with inconclusive findings. In the present study, 106 heroin addicts (West European, Caucasians) and 70 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. The frequency of KOR 36G > T SNP was significantly higher among heroin-dependent individuals compared with control subjects (Fisher's exact = 0.044; Pearson chi(2) = 4.2734, P = 0.039; likelihood ratio chi(2) tests = 4.6156, P = 0.032). Although KOR silent polymorphisms may apparently have no consequences on mRNA transcription, post-transcriptional mechanisms, such as mRNA stability, translation efficiency, and regulability may impair the function of kappa receptors system, with increased risk for substance use disorders. In specific, the neurobiological changes induced by mu-kappa opioid imbalance could underlie vulnerable personality traits and risk behavior.

OBJECTIVE: To describe some biological, behavioural and psychological correlates of the Three-Factor Eating Questionnaire, and to determine the relationship between dietary restraint, binge eating, and leptin among obese women seeking treatment. DESIGN: Consecutive series of obese women enrolled in a clinical program for weight reduction treatment. SUBJECTS: Forty-two obese women. Eight participants met the criteria for`severe binge eating' as measured by the Binge Eating Scale. MEASUREMENTS: Energy intake, resting energy expenditure, body composition, leptin, restraint, disinhibition, hunger and binge eating were assessed before starting the treatment. RESULTS: In this sample both higher disinhibition and hunger scores were associated with greater binge eating severity. Obese women with severe binge eating had lower restraint, higher disinhibition and hunger scores, as well as higher daily fat intake, when compared with obese non-binge-eaters. Interestingly, restraint scores were negatively associated with leptin levels among subjects with severe binge eating. CONCLUSION: In obese women with severe binge eating, the negative relationship between dietary restraint and serum leptin concentrations seems mediated by a greater fat intake. These ®ndings need to be veri®ed in further human studies.

Mice pups were exposed daily to a stress-producing procedure (handling and saline injection) during the first 3 weeks of life. At 25 and 45 days of age, they were tested for differences in the tail-flick and hot-plate tests. The results indicate that chronic handling procedures during developmental stages can produce a long-lasting increase of the threshold for painful stimuli. This phenomenon is completely prevented by naloxone pretreatment and has enhancing effects on morphine analgesia, thus suggesting that postnatal handling can exert long-lasting interference on the sensitivity of some opioid receptor populations.

1 Mild stress plus mild pain (solvent injection) applied daily to neonatal mice induces hormonal, behavioural and metabolic changes perduring in the adult life. 2 We investigated whether daily mild stress to neonatal mice induces also long-term de®ned changes of immune response, and whether immune changes are prevented through repeated administration of the opioid antagonist naloxone. 3 Mild stress plus solvent injection administered from birth to the 21st postnatal day causes not only behavioural and metabolic changes, but also long-term (up to 110 days of life) splenocytes modi®cations, consisting in: increased release of the Th-1 type cytokines interleukin-2 (IL-2) (from an average of 346 to 788 pg ml 71 ), interferon-g (from 1770 to 3942) and tumour necrosis factor-a (from 760 to 1241); decreased release of the Th-2 type cytokines IL-4 (from 49.1 to 28.4) and IL-10 (from 1508 to 877). Moreover, enhanced natural killer-cell activity; enhanced proliferative splenocytes properties in resting conditions and following phytohemoagglutinin and concanavalin-A stimulation are observed. Immunological, behavioural and metabolic changes are prevented by the opioid antagonist (7)naloxone (1 mg kg 71 per day s.c., administered instead of solvent) but not by the biologically inactive enantiomorph (+)naloxone. 4 In conclusion, endogenous opioid systems sensitive to naloxone are involved in long-lasting enhancement of the Th-1 type cytokines and cell-mediated immunological response caused by repeated mild stress administered postnatally.