title: Attenuation of methylphenidate-induced tolerance on cognition by buspirone co-administration.
abstract: 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 somatodendritic 5HT-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 methylphenidate-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-HT 1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD.
authors.affiliation: Department of Pharmacology, Federal Urdu University of Arts, Science and Technology, Gulshan-e-Iqbal, Karachi, Pakistan.
authors.forename: Nausheen
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Pharmacology, University of Karachi, Karachi, Pakistan.
authors.forename: Rahila
authors.initials: R
authors.lastname: Najam
authors.affiliation: Department of Pharmacology, University of Karachi, Karachi, Pakistan.
authors.forename: Saira Saeed
authors.initials: SS
authors.lastname: Khan
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001362:Avoidance Learning / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004361:Drug Tolerance; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D044282:Receptor, Serotonin, 5-HT1A; D008774:Methylphenidate; D002065:Buspirone