Cognitive-enhancing activity of thymol and carvacrol in two rat models of dementia

This study evaluated the efficacy of thymol and carvacrol against cognitive deficits induced by amyloid beta (A beta) or scopolamine. Rats received bilateral intrahippocampal injections of A beta(25-35) or intraperitoneal injections of scopolamine, and the effect of different doses of thymol, or carvacrol (0.5, 1, or 2 mg/kg) on cognitive function was determined. Animals were subjected to 5 days of training in the Morris water maze: 4 days with an invisible platform to test spatial learning and the 5th day with a visible platform to test motivation and sensorimotor coordination. The acute toxicities of thymol and carvacrol were also studied. The results showed increases in escape latency and decreases in target quadrant entries in A beta or scopolamine-treated groups. These impairments were reversed by pretraining administration of either thymol or carvacrol. The calculated LD50's of thymol (565.7 mg/kg) and carvacrol (471.2 mg/kg) were found to be much higher than their therapeutic doses (thymol 0.5 mg/kg, carvacrol 1 mg/kg). These findings provide preliminary positive evidence for the effectiveness and safety of thymol and carvacrol in alleviating cognitive impairments caused by increased A beta levels or cholinergic hypofunction. Anticholinesterase, antioxidant, and anti-inflammatory activities may be the mechanisms contributing toward their beneficial effects in these models. Behavioural Pharmacology 23: 241-249 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.