Involvement of histaminergic mechanisms in the potentiating effect of clonidine on pentobarbitone sleep in mice

Intraperitoneally administered clonidine was found to prolong pentobarbitone sleeping time in mice. This effect of clonidine, though effectively antagonised by ip and icv administered chlorpheniramine, a H1 receptor blocker, and yohimbine,an (2 adrcnoceptor blocker, was not antagonised by ip and icv injected mctiamide, a H2 receptor blocker, and prazosin, an (1adrenoceptor blocker. Further, pretreatment with L-histidine, a precursor of brain histamine, and amodiaquine, an inhibitor of histamine N-methyl trausferase, in doses which had no significant per se effect on pentobarbitone-induced sleep, were found to significantly increase the effect of clonidine on pentobarbitone sleep. The results with chlorpheniramine, L-histidine and amodiaquine suggest an involvement of histamine in the potentiating effect of clonidine on pentobarbitone sleep. As the potentiation of pentobarbitone sleep by ip clonidine was antagonised by icv injected chlorpheniramine it suggests that activation of central H1 receptor mechanisms is responsible for the potentiating effect of clonidine on pentobarbitone sleep. Further, as icv injected yohimbine also antagonised the potentiating effect of ip clonidine on pentobarbitone sleep it suggests that the interaction of clonidine with the central histaminergic mechanisms is mediated through specific as adrenoceptors.