Reserpine enhances amphetamine stereotypies without increasing amphetamine-induced changes in striatal dialysate dopamine

Indirect evidence suggests that amphetamine (AMPH) releases dopamine (DA) from an extravesicular, cytoplasmic pool. Disruption of vesicular DA storage by reserpine has been hypothesized to increase the concentration of extravesicular DA available for release by AMPH, which is consistent with the observation that reserpine does not prevent but augments the behavioral response to AMPH. In order to more directly test this hypothesis, the in vivo microdialysis technique was used to concurrently examine the behavioral and striatal dopaminergic response to AMPH (1.25 or 2.5 mg/kg) 24 h following reserpine pretreatment (2.5 mg/kg). Reserpine decreased tissue levels of DA by approximately 90% and reduced baseline dialysate DA concentrations by approximately 80%. Reserpine augmented the behavioural effects of AMPH, particularly increasing the occurrence and intensity of stereotypies. In contrast, reserpine did not alter the amount or duration of AMPH-induced DA release. This observation confirms that DA release by AMPH does not depend on vesicular stores but is inconsistent with the hypothesis that augmentation or behaviour by reserpine results from increased striatal DA release.     

Co-localization of SCPB-like and FMRFamide-like immunoreactivities in crustacean nervous systems

A monoclonal antibody to the molluscan small cardioactive peptide SCPB and a polyclonal antibody to FMRFamide were used to localize antigens in the stomatogastric nervous system and brain of two species of Cancer. Both antibodies labeled cell bodies, axons, and neuropilar processes in the brain and in the stomatogastric nervous system. All of the SCPB immunoreactive neurons were co-labeled with antibody to FMRFamide. However, antibody to FMRFamide labeled additional neurons of the commissural ganglion and the brain that were not immunoreactive to the monoclonal SCPB antibody.     

The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice

Summary:  Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.     

The role of insurance data in setting priorities for netball injury prevention strategies

The aim of this study was to investigate insurance records for a one-year period to determine the injury frequencies and costs associated with different age groups in netball. The insurance records for all netball claims made during 1999 in Victoria were obtained from the insurer and entered into a database. The overall injury rate was 9.49 injuries per 1000 players, with 829 claims for injuries filed with the insurance company. Of all injuries claimed for, 85.3% were to the lower limb, 8.7% to the upper limb, 3.1% to the spine/torso and 2.9% to the head and face. Lower limb injuries accounted for 85.4% of costs, upper limb injuries 10.7% and head/neck/torso injuries 3.9% of total injury costs. Knee injuries accounted for 56.9% of total costs, with ankle and calf/Achilles injuries costing 12.7 and 11.8% of total costs, respectively. Injury prevention strategies should therefore be directed to three main injuries taking into account costs and incidence. These injuries were: ankle sprains, knee ligament sprains and Achilles tendon strains. Specifically, the prevention program for Achilles injuries should be directed to the >25 years age groups.     

Differential loss of neuromuscular connections according to activity level and spinal position of neonatal rabbit soleus motor neurons

We have tested whether the ability of synapses to compete for occupancy of endplates during neuromuscular synapse elimination is affected by differences in the spinal position or in the activity level of the parent motor neuron. To test the role of spinal position, the relative sizes of motor units for motor neurons from middle and extreme (rostral/caudal) positions in the rabbit soleus motor pool were determined at 3 postnatal ages: 4-5 d ("early" ages, when the soleus is heavily polyinnervated), 8-9 d ("intermediate"), and 11-15 d ("late," when the soleus has just reached singly innervated state). Average motor unit sizes from extreme ventral roots were similar to those from middle ventral roots in early-aged soleus muscles but were significantly smaller (by 18-27%) for both intermediate and late muscles. Thus, motor neurons from extreme positions evidently compete less effectively for retention of synapses than those from middle positions. To test the role of differential activity, inactive and active synapses were pitted directly against one another by implanting Silastic plugs laden with tetrodotoxin (TTX) into one of the spinal nerves containing a minority of the soleus motor axons. Differential activity was maintained during a period of extensive synapse loss, from the time of the implant at day 4 or 5 until the intermediate age (day 8-9). Motor unit twitch tensions were subsequently measured to determine the relative number of synapses retained by individual active and inactive motor neurons. The inactivated motor units were on average significantly larger (by more than 50%) than the corresponding group from normal and control-implanted animals. The abnormally large size of inactivated motor units persisted in animals allowed to recover from the TTX block and examined after multiple innervation had disappeared. Hence, the effect of the TTX block cannot be attributed to a simple slowing of synapse elimination specifically among the inactive motor neurons. We conclude that complete presynaptic inactivity improves the chances of survival relative to that for normal activity during synapse elimination in the neonatal rabbit soleus muscle. This difference in competitive ability may contribute to the development of an important characteristic of adult muscles, the correlation between motor unit size and recruitment threshold.     

The effects of clonidine and yohimbine on human information processing

The effects of clonidine and yohimbine on human information processing were tested in six normal volunteers ages 18–30 years. Subjects were tested in a pre-post design with sessions conducted at weekly intervals. Three drug conditions were: Placebo (lactose), 0.2 mg clonidine, and 30 mg yohimbine. Two choice reaction time (RT) tasks were used. One was a stimulus evaluation-response selection task (SERS) that has been shown to be sensitive tod-amphetamine, methylphenidate and scopolamine. The other task was to assess stimulus pre-processing and used spatial frequency as a discriminative stimulus. The principle finding was that clonidine slowed RT; this effect was significant for both tasks. In contrast, yohimbine tended to speed RT, but the effects were significant only for the spatial frequency task on some analyses while not for others. RTs to high spatial frequency stimuli were speeded more than for low spatial frequency. The effects of these two NE drugs were compared with findings withd-amphetamine and scopolamine and interpreted within the framework of a serial information processing model proposed by Callaway (1983). Specifically, it is suggested that yohimbine and clonidine affect an early pre-processing stage.