Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1995-09, Vol.52 (1), p.119-124
• Main Authors: Sudha, S., Lakshmana, Madepalli K., Pradhan, N.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; AChE activity; Animals; Avoidance Learning - drug effects; Biogenic Monoamines - metabolism; Biological and medical sciences; Brain - drug effects; Brain - enzymology; Brain Chemistry - drug effects; Drug toxicity and drugs side effects treatment; Learning; Learning Disorders - chemically induced; Learning Disorders - psychology; Male; Maze Learning - drug effects; Medical sciences; memory; Memory Disorders - chemically induced; Memory Disorders - psychology; Monoamines; Pharmacology. Drug treatments; Phenytoin; Phenytoin - pharmacology; Plasma DPH levels; Rats; Rats, Wistar; Toxicity: nervous system and muscle
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(95)00059-6

Groups of adult, male, Wistar rats were administered phenytoin (DPH) at 5, 12.5, 25, 50, or 75 mg/kg IP for 21 days. The learning and memory of these rats were assessed using the T-maze and passive avoidance tests. The plasma DPH levels, acetylcholine esterase (AChE) activity in different brain regions, and the levels of monoamines in the hippocampus were measured. The results indicate that DPH below the therapeutic plasma level did not significantly impair learning and memory. Correspondingly, no changes were noted in the brain 5-HT or AChE activity. However, DPH, at therapeutic plasma concentrations (i.e., 10.5 μ/ml and 14 μg/ml in the dosage range of 50 and 75 mg/kg, respectively), significantly impaired learning and memory in rats. The impaired learning and memory functions were associated with increased 5-HT levels and decreased AChE activity in the hippocampus. With a dose of 75 mg/kg DPH, there was a reduction in the AChE activity in the striatum, in addition to hippocampus. It is conjectured that the neurochemical changes brought about by DPH at therapeutic plasma levels may account for the impairment of learning, memory, and cognitive functions in epilepsy.