Serotonergic receptor antagonists alter responses to general anaesthetics in rats

Serotonergic neurotransmission is involved in controlling arousal levels in humans and other animals. Here, the effects of serotonergic receptor antagonists on the induction and depth of anaesthesia produced by three different general anaesthetics were investigated. Rats were pretreated (i.p.) with either methiothepin (1.5 mg kg(-1)), mianserin (5 mg kg(-1)), ketanserin (7 mg kg(-1)) or saline. Subsequently, successive, cumulative doses (i.p.) of either ketamine (final, cumulative dose of 350 mg kg(-1)), sodium pentobarbital (final dose 77 mg kg(-1)), or chloral hydrate (final dose 600 mg kg(-1)) were administered. The response to the anaesthetics was measured using a behavioural test battery assessing nocifensive reflexes and hypnotic state. Pre-treatment with methiothepin enhanced responses to all three anaesthetics; mianserin enhanced responses to chloral hydrate. These results show that some serotonergic receptor antagonists change anaesthetic requirements, resulting in enhanced anaesthesia to hypnotics with different mechanisms of action.