The anticonvulsant and behavioral effects of phencyclidine and ketamine following chronic treatment in rats

The effects of chronic phencyclidine (PCP) or ketamine (KET) on their respective acute behavioral and anticonvulsant actions were investigated. Female rats were treated for 15 days with twice daily i.p. injections of saline, 20 mg/kg PCP or 40 mg/kg KET. Subjects treated chronically with PCP were challenged with either 10 mg/kg or 20 mg/kg i.p. PCP, while subjects treated chronically with KET were challenged with 40 mg/kg i.p. KET only. Neither chronic drug treatment induced tolerance to the acute anticonvulsant effect, nor to hyperlocomotion and stereotypy as measured by automated activity monitors. However, evidence of tolerance to the stereotypy induced by acute KET was obtained when an observer-based rating scale was employed. In addition, tolerance occurred to the ataxia induced by KET and the 10 mg/kg, but not 20 mg/kg, dose of PCP. Thus, tolerance occurs to some of the acute behavioral effects of PCP and KET while the anticonvulsant action of these compounds remains unaffected.