Mechanisms of general anesthesia: brain regional responses to baclofen

The GABAB agonist baclofen is reported to produce general anesthesia when administered either centrally into the lateral ventricles of rats or peripherally to mice. Previously we demonstrated that beta-endorphin given intracerebrally produces anesthesia in rats, a response localized to sites in or adjacent to the inferior third and fourth ventricles. In order to compare the anatomical localization of these two anesthetic responses, we administered baclofen into the inferior or superior lateral or third ventricles, the aqueduct, or fourth ventricle in rats. Although 10 micrograms baclofen infusions into several regions caused loss of the righting reflex, in no case did animals exhibit an unconscious state which satisfied strict criteria of anesthesia. Infusions of 20 micrograms into the inferior third and fourth ventricles elicited seizures followed by a postictal depression. Although unresponsive to some stimuli, these animals showed no impairment in the corneal reflex. Since this dose was often lethal, higher doses not tested. Baclofen, given to mice intraperitoneally at doses of 25, 50, or 75 mg/kg, failed to elicit strictly defined anesthesia, although, to varying degrees, animals exhibited analgesia, loss of the righting reflex, and loss of behavioral responses to loud sounds. Animals continued to show motor responses when handled and retained corneal reflexes. Baclofen does not evoke an unconscious anesthetic state when administered centrally or systemically, emphasizing the need for strict criteria to define general anesthesia and to categorize drugs that promote this state.