Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system.

Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity ("incubation") is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective serotonin (5-HT) 5-HT2C​ receptor (5-HT2CR) agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity.

Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity.

Cocaine dependence remains a challenging public health problem with relapse cited as a major determinant in its chronicity and severity. Environmental contexts and stimuli become reliably associated with its use leading to durable conditioned responses ('cue reactivity') that can predict relapse as well as treatment success. Individual variation in the magnitude and influence of cue reactivity over behavior in humans and animals suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse. In the present translational study, we investigated the contribution of variation in the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system in individual differences in cocaine cue reactivity in humans and rodents. We found that cocaine-dependent subjects carrying a single nucleotide polymorphism (SNP) in the HTR2C gene that encodes for the conversion of cysteine to serine at codon 23 (Ser23 variant) exhibited significantly higher attentional bias to cocaine cues in the cocaine-word Stroop task than those carrying the Cys23 variant. In a model of individual differences in cocaine cue reactivity in rats, we identified that high cocaine cue reactivity measured as appetitive approach behavior (lever presses reinforced by the discrete cue complex) correlated with lower 5-HT2CR protein expression in the medial prefrontal cortex and blunted sensitivity to the suppressive effects of the selective 5-HT2CR agonist WAY163909. Our translational findings suggest that the functional status of the 5-HT2CR system is a mechanistic factor in the generation of vulnerability to cocaine-associated cues, an observation that opens new avenues for future development of biomarker and therapeutic approaches to suppress relapse in cocaine dependence.

Blockade of the serotonin 5-HT2A receptor suppresses cue-evoked reinstatement of cocaine-seeking behavior in a rat self-administration model.

The serotonin 5-HT2A receptor (5-HT-sub(2A)R) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT-sub(2A)R antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in naïve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT-sub(2A)R antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT-sub(2A)R attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse.

Hearing where we're coming from--ethically and professionally.

Anthropologists concerned about the discipline's ability to cope ethically and ethnographically with a globalized world should not dismiss too hastily the methodology--and the ethics built into it--that anthropology developed over the last century. This methodology of making "displacing" translations, based on ethnographic experience and a politics of translation, can still provide a workable ethics and a viable labor of ethnography even in the world at present.

[Incidence of postmyelography syndrome and postmyelography complaints after lumbar puncture with the Sprotte pencil-like needle in comparison with the Quincke needle]. / Inzidenz des Postmyelographiesyndroms (PMS) und postmyelographischer Beschwerden nach lumbaler Punktion mit der bleistiftförmigen Nadel nach Sprotte im Vergleich zur Nadel nach Quincke.

PURPOSE: Myelography in combination with a postmyelography CT is an important presurgical examination because of its excellent visualisation of the disc, the bone and the contrast-filled dura. Side effects after myelography can be observed in up to 50% of patients. The pathophysiological mechanism is thought to be increased cerebrospinal fluid leakage at the puncture site. Since the introduction by Sprotte in 1979 of the pencil-point needle, a modification of Whitacre's needle, fewer complaints after lumbar puncture have been reported. The aim of the study was to examine the influence of two types of needle points and the temperature (37 degrees C vs 21 degrees C) of the contrast medium (CM; iotrolan, Isovist) on the incidence of side effects of lumbar puncture for myelography. MATERIAL AND METHODS: In a prospective randomized trial the incidence of complaints after lumbar puncture with intrathecal CM application was evaluated by the use of a 21-G pencil-point needle as modified by Sprotte compared to our usual 22-G needle with a Quincke bevel. Some 412 patients (201 female, 211 male; mean age 54.05 +/- 7.4 years) were investigated. Directly after examination and 1. 3 and 5 days later the patients were questioned about complaints (headache, neck stiffness nausea, vomiting, buzzing in the ear and dizziness). The results were tested by the chi square test. RESULTS: A significantly lower incidence of complaints was seen after lumbar puncture with the pencil-point needle/Quincke needle (headache: 6.3%/18.9%, P < 0.0001; headache lasting 3 days: 0.5%/7.8%, P < 0.0001; headache lasting 5 days: 0%/2.4%, P = 0.0305; nausea: 0%/4.9%, P = 0.0009; vomiting: 0%/3.4%, P = 0.0009; dizziness: 0%/3.4%, P = 0.0074; neck stiffness: 0%/3.4%, P = 0.0074). The temperature of the CM had no influence on the complaints. No influence was seen on the quality of the myelogram. No relation to sex and age was found. CONCLUSION: Complaints after lumbar puncture and myelography are caused by the cerebrospinal fluid leakage at the puncture site. The incidence of side effects related to this leakage can be reduced by using a pencil-point needle. The temperature of the CM has no influence on the complaints.

Effect on herd health and productivity of controlling tsetse and trypanosomosis by applying deltamethrin to cattle.

A large cattle ranch was established in 1954 in a heavily tsetse infested part of north-east Tanzania. Trypanosomosis was controlled for 30 years by prophylactic drugs but in 1988 drug resistance seemed to be developing as cases of trypanosomosis were being confirmed 4 or 5 weeks after treatment with isometamidium chloride (Samorin). Herd health had deteriorated and productivity was uneconomically low. In order to control the tsetse population the 8,000 cattle, grazing over 250 km2, were regularly dipped in the synthetic pyrethroid deltamethrin (Decatix Cattle Dip and Spray formulation). Within a year the tsetse population, as monitored by traps, had decreased by more than 90%. Disease mortality decreased by 66% and a range of productivity measures such as calving percentages and weaning weights were raised to levels above those prevailing before the decline in herd health.

An approach-avoidance motivations scale for sports.

The purpose of this study was to construct a motivations scale for sports based on Nygard and Gjesme's Achievement Motives Scale. A test-retest reliability assessment was conducted on an original 36 item pool. Twenty-eight items were interpreted similarly in excess of 64% of test cases. Content validity and objectivity assessments retained the 28 items in the final versions of the questionnaire. The scale was intended for use in athletic environments for the purpose of measuring levels of motivation to approach success and motivation to avoid failure in training, competition, and the general sporting activity. Standardized administration procedures were developed to be followed when using the tool. An evaluation of the usefulness of the scale was provided. Male (N = 90) and female (N = 86) swimmers at the 1977 Canadian Winter Swimming Championships were compared on the basis of the relationship between approach-avoidance factors and a competition performance index. The related factors were totally different between the groups. A suggestion was made that the aspects of achievement motivation assessed by the tool provided different interpretations of the sporting experience for male and female swimmers. The developed scale was reliable, valid, objective, standardized and useful.