SUMMARY1. In high decerebrate rabbits, cells were sampled extracellularly from the rostral flocculus. Purkinje cells were identified by their characteristic responses to stimulation of the contralateral inferior olive. Identification of basket cells was based on the absence of olivary responses and also on their location in the molecular layer adjacent to identified Purkinje cells. Mass field potentials in the flocculus were also studied.2. Single pulse stimulation of a vestibular nerve, either ipsilateral or contralateral, at a rate of 2/sec excited Purkinje cells with a latency of 3-6 msec. This early excitation represents activation through vestibular mossy fibres, granule cells and their axons (parallel fibres). Similar early excitation also occurred in putative basket cells.3. Conjunctive stimulation of a vestibular nerve at 20/sec and the inferior olive at 4/sec, for 25 sec per trial, effectively depressed the early excitation of Purkinje cells by that nerve, without an associated change in spontaneous discharge. The depression recovered in about ten minutes. This recovery was followed by the onset of a slow depression lasting for an hour.4. Conjunctive vestibular-olivary stimulation produced no such depression in the following responses: early excitation in Purkinje cells induced from the vestibular nerve not involved in the conjunctive stimulation; early excitation in putative basket cells from either vestibular nerve; inhibition or rebound facilitation in Purkinje cells following the early excitation; vestibular-evoked field potentials in the granular layer and white matter of the flocculus. These observations lead to the conclusion that the depression occurs specifically at parallel fibre-Purkinje cell synapses involved in conjunctive stimulation.5. Ionophoretic application of glutamate to Purkinje cells in conjunction with 4/sec olivary stimulation depressed the glutamate sensitivity of Purkinje cells; aspartate sensitivity was depressed to a much lesser degree. The depression diminished in about 10 min, but this recovery was succeeded by a slow depression lasting

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Mitragynine, a major constituent of the young leaves of Mitragyna speciosa KORTH., has been reported to exert antinociceptive activity in mice. To determine the mechanism the influence of mitragynine on cAMP content was measured in NG108-15 cells which possess delta opioid receptors and alpha 2B-adrenoceptors. Mitragynine inhibited the forskolin-stimulated cAMP content in a concentration dependent manner as well as morphine and noradrenaline. Mitragynine- and morphine-induced inhibition of cAMP content were blocked by naloxone. Although idazoxane inhibited noradrenaline-induced inhibition of the cAMP content, idazoxane had no effect on mitragynine-induced inhibition. These results suggest that mitragynine acts directly on opioid receptors, but not on alpha 2-adrenoceptors, to show antinociceptive activity.

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