The interaction between pilocarpine and hexobarbital in male rats

Abstract

The interaction between pilocarpine and hexobarbital was studied in male rats. Hexobarbital was infused continously. The dose needed to obtain an EEG criterion (the "silent second") was determined. The ensuing anesthesia times after these equi-anesthetic doses were also recorded. At different times prior to the hexobarbital threshold determination the rats were pretreated with 25-200 mg/kg of pilocarpine. In most experimental series pretreatment with methylatropine (2 mg/kg s.c.) was also given to reduce the effects of pilocarpine on peripheral cholinergic sites. In the dose-response study pilocarpine was given 1 h prior to the hexobarbital threshold determination. Pilocarpine in doses of 25-50 mg/kg increased the amount of hexobarbital needed to obtain the "silent second". With higher doses of pilocarpine, increases in hexobarbital thresholds were seen if no convulsion had been induced by the pilocarpine treatment. If a convulsion was recorded the dose of hexobarbital was reduced. Similar results were obtained in the time-effect studies where more convulsions tended to appear if the time between the dose of pilocarpine and the dose of hexobarbital was increased. In animals without convulsions the effect of pilocarpine on the dose of hexobarbital was counteracted by atropine (8 mg/kg i.p.). The ensuing anesthesia times were increased in the pilocarpine pretreated animals, which could be due to either the pilocarpine dose, the increased dose of hexobarbital needed to obtain the "silent second", or both. No regression between body temperature and dose of hexobarbital was found, but there was a regression with the ensuing anesthesia times. The effects of pilocarpine with an increase in hexobarbital threshold is similar to the changes seen in the threshold in the abstinence after chronic barbital treatments. More important, however, is that both increases are reduced by convulsions. Could pilocarpine be a model for the changes in the abstinence after barbital?