Attenuation of methylphenidate-induced tolerance on cognition by buspirone co-administration

作者：Alam Nausheen^*; Najam Rahila; Khan Saira Saeed

来源：Pakistan Journal of Pharmaceutical Sciences, 2015, 28(5): 1601-1605.

• Methylphenidate
• buspirone
• cognition
• passive avoidance test
• water maze test
• 5HT1A receptors

Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic5HT-(1A)receptors effectiveness. Repeated buspirone administration attenuates 5-HT1A soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce tnethylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone co-administration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD.

• 出版日期2015-9