Some general anesthetics reduce serotonergic neocortical activation and enhance the action of serotonergic antagonists.

In urethane-anesthetized rats, neocortical LVFA induced by 100 Hz electrical stimulation of the median raphe area or by tail pinching was completely eliminated by a combination of scopolamine (5 mg/kg, IP) and p-chlorophenylalanine (500 mg/kg/day x 3, IP), providing evidence that LVFA is dependent on cholinergic-muscarinic and serotonergic inputs to the neocortex in urethane-anesthetized as well as in freely moving rats. The serotonergic receptor antagonists ketanserin and methiothepin (1-10 mg/kg, IP) also produced a dose-dependent blockade of LVFA in urethane-anesthetized rats, and eliminated virtually all LVFA when combined with scopolamine. A combination of diethyl ether anesthesia and scopolamine completely eliminated all neocortical LVFA without additional antiserotonergic treatment, and a combination of chloral hydrate anesthesia and scopolamine similarly blocked all LVFA in about 50% of the rats tested. In the remaining chloral hydrate-anesthetized rats, the residual LVFA could be eliminated by the serotonergic antagonist ritanserin (10 mg/kg, IP). As shown previously, in nonanesthetized rats treated with scopolamine, LVFA can be maintained by a serotonergic input to the neocortex. The present data suggest that some general anesthetics reduce or completely abolish this serotonergic LVFA. Further, the serotonergic antagonists used here exert much stronger antiserotonergic effects in rats anesthetized with urethane or chloral hydrate than in freely moving rats. Therefore, studies of serotonergic transmission or antagonist action, especially in the neocortex, in anesthetized rats may not be applicable to the waking state.