title: Attenuation of methylphenidate-induced sensitization by co-administration of buspirone.
abstract: Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD (attention deficit hyperactivity disorder), but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine (5-HT)-1A somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day enhanced motor activity in home cage i.e. activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13th day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10 mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD.
authors.affiliation: Department of Pharmacology, Federal Urdu University of Arts, Sciences and Technology, Gulshan-e-Iqbal, Karachi, Pakistan.
authors.forename: Nausheen
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: Rahila
authors.initials: R
authors.lastname: Najam
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy & Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Naeem
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004334:Drug Administration Schedule; D008774:Methylphenidate / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D017366:Serotonin Receptor Agonists; D008774:Methylphenidate; D002065:Buspirone