NOx- concentrations in the rat hippocampus and striatum have no direct relationship to anaesthesia induced by ketamine

Abstract

Using microdialysis, we have examined the effects of ketamine on concentrations of total nitric oxide oxidation products (NOx-) in the rat hippocampus and striatum in vivo to investigate the relationship between anaesthesia and NOx- production in the brain. Ketamine 25, 50 and 100 mg kg-1 i.p. increased NOx- concentrations to mean 125 (SD 13)%, 165 (11)% and 193 (13)% of basal, respectively, in the hippocampus and to 122 (12)%, 147 (7)% and 177 (14)% of basal in the striatum. Local perfusion with ketamine 50 and 100 mumol litre-1 into the hippocampus or striatum increased NOx- concentrations to 212 (32)% and 291 (17)% of basal, respectively, in the hippocampus and to 148 (20)% and 201 (18)% of basal in the striatum. Ketamine 50 and 100 mg kg-1 i.p. caused dose-dependent prolongation of loss of the righting reflex (LRR) and 100 mg kg-1 i.p. also caused loss of the corneal reflex (LCR). Local perfusion of ketamine did not provoke LRR or LCR. Inhibition of NOS by L-NAME 100 mg kg-1 i.p. decreased hippocampal NOx- concentrations to 58 (7)% of basal and did not provoke LRR or LCR. Although the effect of ketamine-induced increases in hippocampal NOx- concentrations was significantly depressed by L-NAME, LRR was not affected. These data imply that NOx- concentrations in the hippocampus or striatum have no direct relationship to the anaesthetic efficacy of ketamine, although this requires further investigation.

Anesthetic Ketamine Impairs Rats' Recall of Previous Information

“…12 In line with this view, neurochemical data demonstrated that application of L-NAME counteracted the increase of nitric oxide plasmatic concentrations that were produced by anesthetic ketamine in the rat hippocampus. 13 Although important differences in experimental settings exist between these studies and our findings, these results further support a role for nitric oxide on ketamine's effects.…”

“…For instance, the nonselective nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methylester (L-NAME), antagonized ketamineinduced analgesia 11 ; and the neuronal NOS inhibitor, 7-nitroindazole, conferred protection against ketamine-induced neurotoxicity in newborn rat forebrain culture. 12 A microdialysis study 13 has demonstrated that L-NAME counteracted the increase induced by anesthetic ketamine of nitric oxide oxidation products in the rat hippocampus. Finally, L-NAME was able to reverse recognition and spatial memory deficits produced by subanesthetic doses (3 mg/kg) of ketamine in rats.…”

Pentobarbital Decreased Nitric Oxide Release in the Rat Striatum but Ketamine Increased the Release Independent of Cholinergic Regulation

“…the actual concentration or amount of nitric oxide products in the brain could not be measured because the rate of recovery of neurotransmitters in perfusate from the extracellular space into a dialyzing probe through the membrane is not predetermined. alternations in recovery or No release might have occurred throughout the study, and consistent increases were found in every experiment, as found in a previous investigation [25]; however, we could not explain the reason for stable intraday changes. in summary, Ket increased No release in the rat striatum.…”

“…on the other hand, PB decreases ach release in both the hippocampus and striatum [18]. although wu et al [25] explained the PB-induced decrease and Ket-induced increase in No release as a result of the change that occurs in ach release in both the hippocampus and striatum, the conclusions were tenuous, especially those related to the striatum.…”

“…Exposure to PB-induced general anesthesia could further modulate the feedback loop, including that for ach release, and regulate the extracellular No concentration. Similarly, another popular intravenous anesthetic, Ket, has been reported to increase the No concentration via an increase in ach release in the brain [25]. however, PB and Ket showed differential effects on ach release in the striatum [18].…”