The benzodiazepine antagonist Ro 15–1788 reverses the effect of methyl-β-carboline-3-carboxylate but not of harmaline on cerebellar cGMP and motor performance in mice

Abstract

The cerebellar cGMP level in mice was decreased in a dose-dependent manner 30 min after diazepam ( ED 50 = 2 mg/kg p.o. ). This effect was reversed by the specific benzodiazepine antagonist Ro 15–1788. Methyl-β-carboline-3-carboxylate (β-CCM) and harmaline increased cGMP. Ro 15–1788 dose dependently counteracted the β-CCM- but not the harmaline-induced increase in cGMP. In the horizontal wire test Ro 15–1788 antagonized the impairment of motor performance induced by β-CCM, but not that induced by harmaline. These findings further support the view that harmaline in contrast to β-carboline-3-carboxylates does not act through benzodiazepine receptors, and that Ro 15–1788 antagonizes only those convulsants and stimulants that act through specific benzodiazepine receptors.