Muscarinic Receptors Mediate Carbachol‐Induced Inhibition of Maximal Electroshock Seizures in the Nucleus Reticularis Pontis Oralis

PURPOSE: Previous reports from this laboratory indicated a role for N-methyl-D-aspartic acid (NMDA) and gamma-aminobutyric acid (GABA) receptors among the neuronal mechanisms of the nucleus reticularis pontis oralis (RPO) that regulate the tonic hindlimb extension (THE) component of maximal electroshock seizures (MESs) in rats. This study was intended to determine the role of cholinergic mechanisms in the RPO regulation of THE. METHODS: Rats were surgically prepared with microinjection guide cannulas for the focal administration of drug solutions directly into the RPO. MES was induced with corneal electrodes. RESULTS: RPO microinjection of carbachol significantly inhibited the incidence of THE. RPO microinjection of atropine by itself had no effect on the seizure response but significantly antagonized the anticonvulsant effect induced by RPO microinjection of carbachol. The selective nicotinic agonist dimethylpiperizinium (DMPP) by itself had no effect on THE. RPO microinjection of 10 ng pertussis toxin by itself had no effect on THE but significantly antagonized the anticonvulsant effect induced by RPO microinjection of carbachol. CONCLUSIONS: RPO microinjection of carbachol inhibited the THE component of MESs in rats. The carbachol effect appeared to be mediated by muscarinic receptors as the anticonvulsant activity was antagonized by atropine, and the selective nicotinic agonist DMPP induced no anticonvulsant activity. Because pertussis toxin acts to inhibit muscarinic receptor-linked G proteins, the pertussis toxin antagonism of carbachol also supports a muscarinic mechanism of action.