Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Oct 2007
Non-nociceptive environmental stress induces hyperalgesia, not analgesia, in pain and opioid-experienced rats.
It is well admitted that stress induces analgesia (SIA) via endogenous opioid release. However, there is evidence that stressful events play a role in the pathogenesis of pain, but little is known about mechanisms underlying such pain vulnerability. Previous studies reported that a single opioid exposure activates NMDA-dependent pronociceptive systems leading to long-term pain vulnerability after analgesia. ⋯ This indicates that low levels of opioids induce opposite effects, that is analgesia vs hyperalgesia dependent on prior life events. In pain and opioid-experienced rats, NMDA receptor antagonists, ketamine or BN2572, completely prevented hyperalgesia when injected just before NNES or fentanyl ULD. This latent pain sensitization model may be important for studying the transition from acute to chronic pain and individual differences in pain vulnerability associated with prior life events.
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Neuropsychopharmacology · Sep 2007
Comparative StudyDSM-IV personality disorders in the National Comorbidity Survey Replication.
The population prevalence of DSM-IV personality disorders (PDs) remains largely unknown. Data are reported here on the prevalence and correlates of clinician-diagnosed Clusters A, B, and C DSM-IV PDs in the general population of the United States. ⋯ Strong Axis I comorbidity raises questions about the somewhat arbitrary separation of PDs from Axis I disorders in the DSM nomenclature. The impairment findings suggest that the main public health significance of PDs lies in their effects on Axis I disorders rather than in their effects on functioning.
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Neuropsychopharmacology · Sep 2007
Gender-dependent association of the functional catechol-O-methyltransferase Val158Met genotype with sensation seeking personality trait.
The gene encoding cathechol-O-methyltransferase (COMT) contains a common functional missense polymorphism (Val158Met) that regulates dopamine in an allele-dependent manner. A pivotal role of dopamine neurotransmission in the prefrontal cortex has been implicated in drug-seeking behavior and related personality traits, such as sensation seeking, with some evidence for a gender-specific association. Here, we tested the hypothesis that the COMT Val158Met polymorphism modulates the personality dimension, sensation seeking, in a gender-dependent manner. ⋯ The Val158Met polymorphism was associated with the sensation seeking personality trait in women only. The highest scores in the sensation-seeking scale and in three of the four subscales were observed in female subjects with the Val/Val genotype relative to women carrying the Met allele. Our results suggest that high COMT enzyme activity associated with the Val allele predisposes to high sensation seeking scores in female subjects and add to increasing evidence for a gender specific role of COMT in normal and dysfunctional behavior.
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Neuropsychopharmacology · Jul 2007
Pharmacological characterization of the receptor mediating the anorexigenic action of the octadecaneuropeptide: evidence for an endozepinergic tone regulating food intake.
Peptides of the endozepine family, including diazepam-binding inhibitor, the triakontatetraneuropeptide, and the octadecaneuropeptide (ODN), act through three types of receptors, that is, central-type benzodiazepine receptors (CBR), peripheral-type (mitochondrial) benzodiazepine receptors (PBR) and a metabotropic receptor positively coupled to phospholipase C via a pertussis toxin-sensitive G protein. We have previously reported that ODN exerts a potent anorexigenic effect in rat and we have found that the action of ODN is not affected by the mixed CBR/PBR agonist diazepam. In the present report, we have tested the possible involvement of the metabotropic receptor in the anorexigenic activity of ODN. ⋯ At the highest concentration tested (1000 ng), cDLOP provoked by itself a significant increase in food intake. Taken together, the present results indicate that the anorexigenic effect of ODN and OP is mediated through activation of the metabotropic receptor recently characterized in astrocytes. The data also suggest that endogenous ODN, acting via this receptor, exerts an inhibitory tone on feeding behavior.
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Neuropsychopharmacology · Jun 2007
Randomized Controlled TrialStriatal vs extrastriatal dopamine D2 receptors in antipsychotic response--a double-blind PET study in schizophrenia.
Blockade of dopamine D2 receptors remains a common feature of all antipsychotics. It has been hypothesized that the extrastriatal (cortical, thalamic) dopamine D2 receptors may be more critical to antipsychotic response than the striatal dopamine D2 receptors. This is the first double-blind controlled study to examine the relationship between striatal and extrastriatal D2 occupancy and clinical effects. ⋯ The two subjects who experienced motor side effects had the highest striatal occupancies in the cohort. Striatal D2 blockade predicted antipsychotic response better than frontal, temporal, and thalamic occupancy. These results, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response, suggest that dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia.