Using in vivo microdialysis, we have investigated the effects of propofol on acetylcholine (ACh) release from various regions of the rat brain. Propofol 25 and 50 mg kg-1 i.p. decreased basal ACh release from the frontal cortex by 70% and 85%, respectively. Propofol 25 and 50 mg kg-1 i.p. decreased basal ACh release from the hippocampus by 47% and 72%, respectively. However, in rat striatum, propofol 25 mg kg-1 i.p. did not affect basal ACh release and 50 mg kg-1 i.p. produced slight inhibition of basal ACh release (by 19%) only in the second sample after i.p. injection. In addition, we also examined the pharmacological mechanisms mediating the interaction between propofol and a gamma-aminobutyric acid A (GABAA) receptor complex. In the rat hippocampus, local application of bicuculline 1 mumol litre-1, a GABAA receptor antagonist, significantly antagonized the inhibitory effects of propofol 50 mg kg-1 i.p. on basal ACh release. In the rat frontal cortex, local application of bicuculline 1 mumol litre-1 did not antagonize the inhibitory effects of propofol 50 mg kg-1 i.p. on basal ACh release, while systemic application of bicuculline 1 mg kg-1 i.p. significantly antagonized the inhibitory effects of propofol 50 mg kg-1 i.p. These results suggest that propofol has powerful depressant effects on ACh release from the rat frontal cortex and hippocampus but not from the striatum, indicating that propofol has a "region-selective" anaesthetic action. Further, these results suggest that the inhibitory effects of propofol in the rat hippocampus may involve "intra" hippocampal GABAA receptors while the inhibitory effects in the rat frontal cortex may be mediated by GABAA receptors other than "intra" frontal cortex GABAA receptors.

We have studied the effects of ketamine and pentobarbitone on acetylcholine (ACh) release from the rat frontal cortex using microdialysis. Ketamine 25, 50 and 100 mg kg-1 increased ACh release from the frontal cortex to 286%, 253% and 381% of basal release, respectively. In contrast, pentobarbitone 10, 20 and 40 mg kg-1 caused 73%, 78% and 96% inhibition of basal levels, respectively. The results suggest that ketamine and pentobarbitone have opposite effects on ACh release from the rat frontal cortex, as seen previously in the rat hippocampus.

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.