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Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages employed may not have been equivalent in efficacy. Future studies are needed to delineate the cognitive and behavioral effects of TPM at lower dosages.

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Background-Clinicians monitor cognitive effects of drugs primarily by asking patients to describe their side effects. We examined the relationship of subjective perception of cognition to mood and objective cognitive performance in healthy volunteers and neurological patients.

SUMMARY1. Adenosine and several of its analogues produced a concentration-dependent shortening of calcium-dependent action potential (c.a.p.) duration of mouse dorsal root ganglion (d.r.g.) neurones in dissociated cell culture. The following rank order of potency was obtained: N6-(L-phenylisopropyl)adenosine > N6-(D-phenylisopropyl)adenosine > N6-cyclohexyladenosine > 2-chloroadenosine > 1-methylisoguanosine > adenosine. Effects of adenosine agonists on c.a.p. duration were blocked by methylxanthine adenosine antagonists. Adenosine monophosphate (AMP) and cyclic AMP shortened c.a.p.s in d.r.g. neurones, while ATP also depolarized cells.2. Voltage-clamp analysis revealed that the effect arose from reduction of a voltage-dependent calcium conductance. Adenosine agonists reduced depolarizationevoked inward currents but did not alter membrane conductance following blockade of calcium channels by cadmium. Additionally, adenosine reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance.3. If effects of adenosine on neuronal somata and synaptic terminals are similar, adenosine agonists may inhibit neurotransmitter release in the central nervous system by inhibiting a voltage-dependent calcium conductance. Since effects of adenosine agonists did not correspond with their relative potencies as modulators of adenylate cyclase activity or inhibitors of neurotransmitter release in peripheral tissues, a novel adenosine receptor may be involved in regulation of this conductance.

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SUMMARY Purpose To investigate the effects of low frequency stimulation (LFS) of a fiber track for the suppression of spontaneous seizures described by Nissinen in a rat model of human temporal lobe epilepsy. Methods Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recordings electrodes were placed in the CA3 regions bilaterally and neural data was recorded for a minimum of six weeks. LFS (60 minute train of 1Hz biphasic square wave pulses, each 0.1ms in duration and 200μA in amplitude, followed by 15 minutes of rest) was applied to the VHC for, two weeks, 24 hours a day. Key Findings The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n=7). By the end of the two-week period of stimulation, there was a significant 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during two weeks LFS session. The hippocampal histological analysis showed no significant difference between rats that received LFS and SE-induction and those that had only received SE-induction. None of the animals showed any symptomatic hemorrhage, infection or complication. Significance LFS applied at a frequency of 1Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could be lead to the development of the new therapeutic modality for human patients with temporal lobe epilepsy.

SUMMARY1. The actions of the opioid peptides dynorphin A and (Leu)enkephalin were assessed on calcium-dependent action potentials and inward calcium currents recorded from somata of mouse dorsal root ganglion (d.r.g.) neurones grown in primary dissociated cell culture. Dynorphin A and (Leu)enkephalin decreased the duration of somatic calcium-dependent action potentials in a portion of d.r.g. neurones impaled with potassium acetate-filled micropipettes. When substantial potassium conductance was blocked by intracellular injection of caesium acetate, d.r.g. neurones continued to respond to dynorphin A but responses to (Leu)enkephalin were abolished.2. In voltage-clamp experiments, dynorphin A but not (Leu)enkephalin reduced the magnitude of inward calcium currents. Dynorphin A responses were blocked by the opiate antagonist naloxone. The dynorphin A effect was due to reduction of voltage-dependent calcium conductance since dynorphin A reduced depolarizationevoked inward currents but did not alter membrane conductance following blockade ofcalcium channels by cadmium, and because dynorphin A reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance.3. Dynorphin A binds with high affinity to K-opioid receptors. (Leu)enkephalin, which has affinity for both It-and s-receptors but not for K-opioid receptors, was without effect on calcium conductance. Therefore, we suggest that K-receptors are coupled to voltage-dependent calcium-channels and that binding of dynorphin A produces a decrease of calcium current.