Dose- and time-dependent effects of ketamine on SI neurons with cutaneous receptive fields.

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Abstract
The effects of systemically administered ketamine on SI neuron spontaneous and stimulus-evoked discharge activity and on receptive field (RF) properties were examined in Macaca fascicularis monkeys. The effects observed in behaving animals do not differ qualitatively or quantitatively from those observed in animals immobilized with gallamine. I.v. or i.m. ketamine in doses above 0.5 mg/kg consistently reduces the mean rate and alters the pattern of spontaneous activity, elevates the minimal strength of von Frey stimulation required to evoke discharge activity, reduces RF size and depresses the mean rate of discharge evoked by suprathreshold punctate or by surface-parallel moving tactile stimuli. All of the observed effects on SI neurons exhibit a dose and time dependency. Ketamine reduced the sensitivity of RI loci by elevating the von Frey threshold and by reducing the response to tactile stimuli. The effect on threshold is most prominent for RF loci located remote to the RF center and least for loci within the RF center. As a consequence of the action on threshold, an RF mapped with a von Frey stimulus of moderate intensity after ketamine administration corresponds to only a fraction of the RF mapped with that same stimulus in the absence of general anesthetic. The effect of a given dose of ketamine on von Frey stimulus threshold at a given FR locus is, to a 1st approximation, proportional to the distance of that locus from the FR center, over the dosage range 0.5-30 mg/kg. The recovery of sensitivity to von Frey stimuli following ketamine administration is characterized by the orderly reemergence of RF loci. Loci nearest to the RF center are the first to recover, while the off-center loci recover more slowly. Doses of ketamine in excess of 7 mg/kg significantly alter the size, configuration and, at times the position of the skin fields providing input to neurons located in laminae II-VI of cytoarchitectural areas 3a, 3b, 1 and 2. Dosage and time after administration ketamine are variables that exert predictable and prominent influences on maps of SI topographic organization reeconstructed from RF observations. Ketamine reduced both the magnitude and the duration of the response evoked from single SI neurons by a tactile stimulus moving at constant velocity over the RF. These effects also exhibit dose and time dependency. The detailed effects of ketamine on the response evoked from an SI neuron by a moving stimulus are only rarely completely predictable from the RF organization determined using von Frey stimuli.