Rapidly recurring cortical seizures induce changes in neuronal responsiveness to acetylcholine.

The majority of mechanisms proposed to explain epileptic discharge suggest an excessive synaptic input into the cell or possible changes in cellular excitability which result in a decreased firing threshold and in the presence of self-sustained activity. It is likely that these changes are caused by modifications in the membrane receptor sensitivity to a specific neurotransmitter. In view of the above, the purpose of the present study has been to evaluate the sensitivity of the postsynaptic receptor by means of the microiontophoretic applications of substances whose pharmacological effect is known, thus determining its possible involvement in the epileptic process. Changes in cortical excitability were induced by electric stimuli in the sensorimotor cortex of rats anesthetized with urethane (1 g/kg intraperitoneally), immobilized with pancuronium bromide and kept alive with mechanical respiration. The electric stimuli consisted of trains of biphasic pulses, each lasting one millisecond, with a frequency of 100 pps and with a train duration of 1 second. The response of the neuron to acetylcholine was evaluated before and after the kindling had been established. The dosage was measured in nanoamperes of microiontophoretic ejecting current. Extracellular field potentials were recorded with the central barrel of 4-barrel micropipettes. Peripheral barrels were used for iontophoretic applications of Acetylcholine (Ach .1, 1M), Atropine (25mM). One of these barrels containing NaCl (2M) was used for the automatic passage of balancing current.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral and biochemical correlates of chronic administration of quipazine.

In Experiment 1 groups of rats received single injections of 1, 3, 10, 20 or 40 mg/kg quipazine, and their total 24-hr food and water intake after a 24-hr deprivation period was recorded; there was a dose-related reduction of both food and water intake. In Experiment 2 a group of 15 rats received 5 mg/kg/day, SC quipazine during 29 days, and a control group received saline injections. During treatment, all animals were exposed to a 24-hr food and water deprivation schedule, alternated with 24 hr of free access. Food and water consumption was measured 2 and 24 hr after drug injection; regional 5-HT concentrations were determined at 1 and 13 treatment days by fluorometric assay. Beginning the first treatment day, food and water intake decreased, but by the 13th day the quipazine group had returned to normal ingestion levels. 5-HT concentrations were increased in cerebellum and cortex in acute conditions, but after 13 days they had decreased in cerebellar samples. In Experiment 3 we found that the effects of quipazine on food and water ingestion were recovered after 14 days of discontinuing chronic drug administration.