Bilateral duplication of the internal auditory canals and bilateral cochlear implant outcomes and review.

OBJECTIVES: Bilateral duplication of the internal auditory canal (IAC) is rare and is associated with profound sensorineural hearing loss. The present study aims to review our experience with bilateral cochlear implantation (CI) in children with a duplication of the IAC and to review the literature. METHODS: The Sydney Cochlear Implant Centre database was searched for children with duplication of the internal auditory canal. Data was collected regarding clinical history, MRI and CT findings, auditory brainstem responses (ABR), tympanometry and otoacoustic emissions (OAE), visually reinforced orientation audiometry, auditory brainstem response, electrocochleography (ECochG), transtympanic electrical auditory brainstem response (ABR), aided cortical evoked potentials (CAEP) and intraoperative neural response telemetry (NRT) and CI evoked electrical auditory brainstem testing. RESULTS: two children with bilateral duplication of the IAC were identified who successfully underwent bilateral cochlear implantation. Audiological development was monitored for 2 and 3 years respectively, both children could spontaneously verbalise and displayed Categories of Auditory Performance (CAP) score of 5 and 6 respectively. CONCLUSION: Children with duplication of the IAC, with accompanying cochlear nerve dysplasia (CND) can benefit from CI surgery, and verbal receptive and expressive language is possible.

Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.

The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats.

Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.

Adolescent rats find repeated Delta(9)-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure.

The current study examined whether adolescent rats are more vulnerable than adult rats to the lasting adverse effects of cannabinoid exposure on brain and behavior. Male Wistar rats were repeatedly exposed to Delta-9-tetrahydrocannabinol (Delta(9)-THC, 5 mg/kg i.p.) in a place-conditioning paradigm during either the adolescent (post-natal day 28+) or adult (post-natal day 60+) developmental stages. Adult rats avoided a Delta(9)-THC-paired environment after either four or eight pairings and this avoidance persisted for at least 16 days following the final Delta(9)-THC injection. In contrast, adolescent rats showed no significant place aversion. Adult Delta(9)-THC-treated rats produced more vocalizations than adolescent rats when handled during the intoxicated state, also suggesting greater drug-induced aversion. After a 10-15 day washout, both adult and adolescent Delta(9)-THC pretreated rats showed decreased social interaction, while only Delta(9)-THC pretreated adolescent rats showed significantly impaired object recognition memory. Seventeen days following their last Delta(9)-THC injection, rats were euthanased and hippocampal tissue processed using two-dimensional gel electrophoresis proteomics. There was no evidence of residual Delta(9)-THC being present in blood at this time. Proteomic analysis uncovered 27 proteins, many involved in regulating oxidative stress/mitochondrial functioning and cytoarchitecture, which were differentially expressed in adolescent Delta(9)-THC pretreated rats relative to adolescent controls. In adults, only 10 hippocampal proteins were differentially expressed in Delta(9)-THC compared to vehicle-pretreated controls. Overall these findings suggest that adolescent rats find repeated Delta(9)-THC exposure less aversive than adults, but that cannabinoid exposure causes greater lasting memory deficits and hippocampal alterations in adolescent than adult rats.

Rapid quantitation of fluoxetine and norfluoxetine in serum by micro-disc solid-phase extraction with high-performance liquid chromatography-ultraviolet absorbance detection.

A rapid, robust and sensitive method for the extraction and quantitative analysis of serum fluoxetine (FLX) and norfluoxetine (N-FLX) using a solid-phase extraction (SPE) column and high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection was developed and validated. The sample clean-up step was performed by simple micro-disc mixed-mode (non-polar and strong cation exchange (SCX)) SPE cartridges. Separation of analytes and internal standard (IS) clomipramine (CLO) from endogenous matrix interference was achieved using a Waters Symmetry C(8) (150 mm x 2.1 mm i.d., 5 microm) reversed-phase narrow bore column. The relative retention times were 8.5, 9.6 and 10.5 min for FLX, N-FLX and CLO, respectively with a low isocratic flow rate of 0.3 ml/min. Chromatographic run time was completed in 15 min and peak area ratios of analytes to IS were used for regression analysis of the calibration curve. The latter was linear from 10 to 4000 nmol/l using 0.5 ml sample volume of serum. The average recovery was 95.5% for FLX and 96.9% for N-FLX. The lowest limit of quantitation (LLOQ) for serum FLX and N-FLX was 10 nmol/l (on-column amount of 200 fmol). The method described was used to analyse serum samples obtained from rats given chronic FLX treatment and to examine the relationship between steady state serum drug concentrations and neurochemical changes in several brain regions.

Chronic fluoxetine treatment partly attenuates the long-term anxiety and depressive symptoms induced by MDMA ('Ecstasy') in rats.

Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 x 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.

Heat increases 3,4-methylenedioxymethamphetamine self-administration and social effects in rats.

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a drug frequently used under hot conditions in nightclubs. In rats tested in the social interaction paradigm, greater prosocial effects of MDMA (5.0 mg/kg) were seen at a hot temperature (30 degrees C) relative to normal laboratory temperature (21 degrees C). In the intravenous drug self-administration paradigm, hot temperature (30 degrees C) increased the number of MDMA infusions (0.1, 0.3 or 1.0 mg/kg/infusion) self-administered by rats. Hot temperatures thus appear to affect both the social and reinforcing effects of MDMA.