A microiontophoretic study of the actions of the putative sleep factor, piperidine, in the rat brainstem.

By means of microiontophoresis, we have compared the actions of a putative sleep substance, piperidine, with other neurotransmitters in the rat anaesthetized with urethane. In the pons and midbrain, piperidine mimicked the actions of acetylcholine on more than 200 neurones. Piperidine- and acetylcholine-induced excitations were equally effectively antagonized by hexamethonium or atropine. In 32 neurones piperidine showed no affinity for the receptors for the excitatory amino acid agonists, quisqualate and N-methyl-D-aspartate, piperidine-evoked excitations being unaffected by the antagonists glutamate diethylester or 2-amino-5-phosphonovalerate. Similarly, piperidine-evoked excitations in 23 neurones were unaffected by alpha-methylnoradrenaline, suggesting that piperidine does not act at receptors for noradrenaline. Twenty per cent of neurones responsive to piperidine were inhibited. These inhibitions in 12 neurones were insensitive to either strychnine or bicuculline indicating that piperidine does not act on receptors for glycine or gamma-aminobutyric acid. In a further 68 neurones, neither hexamethonium (4 out of 59 cells) nor atropine (0 out of 9 cells) was effective in antagonizing the inhibitions evoked by piperidine or by acetylcholine. It is suggested that piperidine may exert its central hypnogenic effects by an action at cholinoceptors in brainstem areas involved in sleep regulation.