An EEG and behavioural study on the interactions of clonidine with phencyclidine and ketamine in rats.

Clonidine, an alpha-2 adrenergic agonist, caused sedation and synchronized brain electrical activity in rats starting at 0.05 mg/kg. At low and moderate doses of the dissociative anesthetics PCP and ketamine, clonidine fully inhibited their EEG and behavioral effects, but at high doses it potentiated them. Yohimbine reversed both the inhibitory and potentiating effects of clonidine, as well as the sedation and EEG synchronization. Prazosin did not produce these effects, indicating alpha-2 adrenoceptors are involved. The interaction between dissociative anesthetics and central adrenergic receptors appears complex, with possible relevance for improving ketamine anesthesia and treating PCP intoxication.

Study at a glance

Abstract

1. Clonidine, an alpha-2 adrenergic agonist, induced in rats a synchronization of the electrical activity of the brain (EEG) accompanied by sedation starting from the dose of 0.05 mg/kg, i.p. 2. This drug (0.05 mg/kg, i.p.) was also able to influence both the EEG and behavioural effects elicited by two "dissociative anaesthetics", PCP and KT. 3. At low and moderate doses of these two drugs, clonidine fully inhibited the EEG and behavioural effects, whereas at high doses of both drugs clonidine potentiated these effects. 4. Yohimbine was able to revert the inhibitory and potentiating effects produced by clonidine. It was also able to revert sedation accompanied by EEG synchronization. 5. Prazosin, on the other hand, was not able to produce such effects. This fact suggests that the alpha-2 adrenoceptors are involved in these effects. 6. Based on our findings, the interaction of the dissociative anaesthetics (PCP-KT) with the central adrenergic receptors seems to be very complex. The possible relevance of clonidine on both the improvement of KT-induced anaesthesia and the treatment of PCP-intoxication is also discussed.