Reduced activity at the 5-HT(2C) receptor enhances reversal learning by decreasing the influence of previously non-rewarded associations.

RATIONALE: Reversal learning deficits are a feature of many human psychopathologies and their associated animal models and have recently been shown to involve the 5-HT(2C) receptor (5-HT(2C)R). Successful reversal learning can be reduced to two dissociable cognitive mechanisms, to dissipate associations of previous positive (opposed by perseverance) and negative (opposed by learned non-reward) valence. OBJECTIVES: This study aims to explore the effect of reducing activity at the 5-HT(2C)R on the cognitive mechanisms underlying spatial reversal learning in the mouse. METHODS: Experiment 1 used the 5-HT(2C)R antagonist SB242084 (0.5 mg/kg) in a between-groups serial design, experiment 2 used 5-HT(2C)R KO mice in a repeated measures design. Animals initially learned to discriminate between two lit nosepoke holes. This was followed by three conditions; (1) full reversal, where contingencies reversed; (2) perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3) learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-. RESULTS: SB242084 treated and 5-HT(2C)R KO mice showed enhanced reversal learning seen as a decrease in trials, correct responses, and omissions to criterion in the full reversal condition. Similar effects were observed in the learned non-reward condition but SB242084 treated and 5-HT(2C)R KO mice did not differ from controls in the perseverance condition. SB242084 treated, but not 5-HT(2C)R KO mice, showed decreases in all latency indices in every condition. CONCLUSION: Reducing activity at the 5-HT(2C)R facilitates reversal learning in the mouse by reducing the influence of previously non-rewarded associations.

A gut feeling about insular seizures.

A 43-year-old man presented to the Prince of Wales Hospital, Sydney, New South Wales, Australia, after experiencing his first tonic-clonic seizure. For the previous 2 years he had undergone gastroenterological investigation of episodes of gagging associated with hypersalivation and lachrymation, occurring three or four times per week. EEG showed epileptiform discharges in the right anterior temporal region; brain MRI revealed a lesion in the right insular cortex. Video-EEG telemetry demonstrated that the episodes of gagging were focal seizures. Antiepileptic drug therapy resulted in no further episodes occurring over the next 10 months.

Intra-accumbens baclofen, but not muscimol, mimics the effects of food withdrawal on feeding behaviour.

Intra-accumbens stimulation of GABA receptors results in a robust increase in food intake. However the differential consequences of stimulating GABA(A) and GABA(B) receptors in the nucleus accumbens have not been extensively explored with respect to feeding behaviour. Here we compare the effects of the GABA(B) receptor agonist baclofen and GABA(A) receptor agonist muscimol, infused into the nucleus accumbens shell, on food intake and related behavior patterns. Baclofen (110-440 ρmol) dose dependently enhanced intake and delayed the onset of satiety within the test period as did the effects of 4-8h food withdrawal. Muscimol (220-660 ρmol) enhanced intake but also disrupted the sequence of associated behaviours at every dose tested. We conclude that GABA(B) receptors in the nucleus accumbens shell may play a role in relation to feeding motivation whereas GABA(A) receptors may, as previously suggested, have a more restricted role in relation to the motor components of approach to food and ingestion.

AUStralian study of titration to effect profile of safety (AUS-STEPS): high-dose gabapentin (neurontin) in partial seizures.

PURPOSE: To evaluate the safety, tolerability, efficacy, and impact on quality of life of gabapentin (Neurontin; GBP) as adjunctive therapy in patients with refractory partial seizures. METHODS: AUS-STEPS was an open-label, multicenter, prospective study in patients experiencing partial seizures who were inadequately controlled with one to three concurrent antiepileptic drugs (AEDs). GBP treatment was titrated to a maximum of 4,800 mg/day, over a treatment period of 24 weeks, to achieve an efficacious and tolerable dosage. Efficacy was assessed by seizure-frequency data. Quality of life was evaluated by using the QOLIE-10 questionnaire, and safety was assessed by adverse-event reports and clinical laboratory findings. RESULTS: A total of 176 patients received treatment with GBP, with 174 evaluable for intention-to-treat (ITT) efficacy analysis. A reduction of >50% in overall seizure frequency was observed in 93 patients (53%). There was a small (4.6%) overall improvement in QOLIE-10 score. The most frequent adverse events were dizziness (31%), fatigue (29%), somnolence (27%), headache (21%), and ataxia (20%), with no major increase seen in adverse events necessitating discontinuation as the dose of GBP was titrated upward. CONCLUSIONS: This study indicates that patients with partial epilepsy may be effectively treated with GBP at dosages of < or =4,800 mg/day, without altering the safety profile of the drug.

Intraaccumbens baclofen selectively enhances feeding behavior in the rat.

Intraaccumbens infusions of the GABA(B) agonist baclofen are known to stimulate food intake in the rat. The aim of the present study was to evaluate the effects of baclofen infusion on nonfood-related chewing and on the consumption of a palatable fluid. Rats were bilaterally infused with baclofen (188 ng in 1 microL) or saline, and tested in a situation in which food was available in one or two locations and wood blocks might also be present. Baclofen-infused animals showed no enhancement of chewing directed at the wood blocks, but showed increased food consumption regardless of food location. In a second, separate test we recorded the microstructural parameters for drinking of a palatable glucose/saccharin mixture. Baclofen infusion had no effect on overall intake, although bout size was reduced and the number of bouts was increased. These data confirm that baclofen-stimulated food intake following accumbens infusion is a robust and substantial phenomenon that appears to be selective to solid food. It is likely to result from relatively direct activation of neural circuits for feeding, rather than an indirect facilitation consequent upon changes in taste processings, as has been suggested for some other examples of drug-induced hyperphagia.

Intractable epilepsy as the initial manifestation of neurosyphilis.

A 29-year-old man experienced intractable partial seizures as the initial manifestation of neurosyphilis. The diagnosis was made after the onset of dementia 9 months later. Both the epilepsy and dementia resolved with penicillin therapy. Syphilis should be considered in patients with adult-onset focal epilepsy, particularly if there is associated dementia. Treatment may be successful even when the diagnosis is delayed.

Little and often: ingestive behavior patterns following hippocampal lesions in rats.

Lesions of both dorsal and ventral hippocampus were produced by multiple infusions of the excitotoxin AMPA. Meal patterns recorded before and after lesioning showed no change in total food intake, but a striking behavioral syndrome in which the lesioned rats took smaller meals 2-3 times as frequently and showed a similar change in drinking. In addition, lesioned rats alternated more frequently between feeding and drinking during a single bout of ingestive behavior. There were no group differences in the satiety sequence that followed a meal. In an open field test, lesioned rats showed enhanced locomotion in the periphery and reduced rearing. An olfactory habituation-dishabituation task showed that the lesioned rats investigated olfactory stimuli less but dishabituation to a changed stimulus was normal. The data are discussed in terms of changes in behavioral switching or a possible interoceptive agnosia following hippocampal damage.

X-linked Dystonia-Deafness syndrome.

We report a family with early-onset deafness and progressive dystonia exclusively involving males over two successive generations. There is also evidence of cognitive impairment and corticospinal tract involvement. The pedigree suggests an X-linked inheritance. A similar family was originally described by Scribanu and Kennedy. Tranebjaerg et al. have recently reported two other families with linkage to Xq22 and also proposed a novel X-linked candidate gene. These findings support the existence of a distinct neurodegenerative syndrome principally characterized by early-onset deafness and progressive dystonia. Neuropathology of one case showed a mosaic pattern of neuronal loss and gliosis in the caudate and putamen suggesting that this pattern is not restricted to XDP or Lubag.

Computed tomography and magnetic resonance imaging of the brain in hypoglycaemic encephalopathy.

A diabetic man suffering from a hypoglycaemic attack presented to our hospital. Magnetic resonance imaging (MRI) findings were grossly abnormal and difficult to interpret. The computed tomographic appearance simulated multiple infarctions. The MRI appearance simulated a space occupying lesion. Literature review of the radiology and the pathophysiology of hypoglycaemic brain damage is provided. Comparison between our findings and previous reports is also given.

Hypnotic induction of an epileptic seizure: a brief communication.

This case study investigated the utility of hypnosis to precipitate a seizure in a patient with refractory epilepsy. The patient was twice administered a hypnotic induction and a suggestion to age regress to a day when he was distressed and suffered repeated seizures. The patient did not respond to the first hypnotic suggestion; however, an epileptic seizure was observed in the second hypnotic session. Videorecording and subdural electroencephalograph recording confirmed that he suffered an epileptic seizure. Postexperimental inquiry revealed that the patient used deliberate cognitive strategies to avoid seizure onset in the first session but adopted a more constructive cognitive style in the second session. Findings are discussed in terms of emotions, hypnosis, and cognitive style as mediating factors in the experimental precipitation of epileptic seizures.

Disturbance of meal patterning following nucleus accumbens lesions in the rat.

In this study, we examined the effects of electrolytic lesions of the nucleus accumbens which had no obvious effect on body weight, or on the short term intake of solid food, sucrose and salt solutions. However in 24 h records of feeding and drinking lesioned animals took many more meals of shorter duration. Challenge with the dopamine D2 antagonist YM-09151-2 resulted in a decrease in feeding rate, together with a facilitation of meal size in drinking, in both control and lesioned subjects.

Corpus callosotomy for intractable epilepsy: seizure outcome and prognostic factors.

We reviewed the outcome of corpus callosal section in 64 adult and pediatric patients to identify factors associated with a good outcome: 48% of patients had a favorable outcome for overall seizure frequency. Improvement was noted in several seizure types and was most likely for drop attacks, particularly in the setting of a unilateral focal cerebral lesion or a true generalized epilepsy of Lennox-Gastaut type. Poor outcomes for drop attacks were more likely if there was associated severe intellectual handicap or bilateral independent spikes on interictal EEG. Complex partial seizures (CPS), most commonly of frontal lobe origin, also responded favorably. The complications of callosal section were usually mild and transient. New focal seizures occurred in only 2 patients and were not as frequent or disabling as preoperative seizures types. A worthwhile improvement in seizure outcome was achieved by completion of the callosotomy in 6 of 10 patients with unsatisfactory results from anterior callosotomy.

Orthostatic transient ischemic attacks: a symptom of large vessel occlusion.

Orthostatic transient ischemic attacks (TIA) are very much rarer than orthostatic generalized cerebral ischemia (syncope). A case is described and previous reports reviewed. Orthostatic TIA appears to occur only with large vessel occlusion. In these patients, collateral blood supply is marginal and unable to support normal postural autoregulation.