Tetrahydropalmatine exerts numerous pharmacological activities, including
analgesic and
narcotic effects;
anti-arrhythmic, blood pressure lowering and cardioprotective effects; protective effects against
cerebral ischemia-
reperfusion injury; inhibition of platelet aggregation; prevention of ulcerative diseases and inhibition of gastric acid secretion; antitumor effects; and beneficial effects on the
withdrawal symptoms associated with
drug addiction. The present study aimed to investigate the protective effects of
tetrahydropalmatine against ketamine‑induced learning and memory impairment in mice. The Morris water maze test and open field test were used to analyzed learning and memory impairment in mice. ELISA kits and western blotting were used to analyze oxidative stress,
inflammation factors, caspease‑3 and caspase‑9, iNOS,
glial fibrillary acidic protein (GFAP), glial cell‑derived
neurotrophic factor (
GDNF),
cytochrome c and
phospholipase C (PLC)‑γ1
protein expression. The results demonstrated that
tetrahydropalmatine treatment significantly decreased escape latency in the learning phase and increased the number of platform site crossings in ketamine‑induced mice. In addition,
tetrahydropalmatine significantly inhibited oxidative stress,
inflammation and
acetylcholinesterase activity, and decreased
acetylcholine levels in ketamine‑induced mice.
Tetrahydropalmatine also suppressed iNOS
protein expression, weakened caspase‑3 and caspase‑9 activation, inhibited nuclear factor‑κB,
glial fibrillary acidic protein,
cytochrome c and
phospholipase C‑γ1
protein expression, and induced glial cell‑derived
neurotrophic factor protein expression in ketamine‑induced mice. Taken together, these results indicated that
tetrahydropalmatine may protect against ketamine‑induced learning and memory impairment in mice via antioxidative, anti‑inflammatory and anti‑apoptotic mechanisms. The present study provided an experimental basis for the clinical application of
tetrahydropalmatine to reduce the severe side effects associated with
ketamine therapy in future studies.