Methylphenidate as a reinforcer for rats: contingent delivery and intake escalation.
Methylphenidate (MPH) is one of the most widely prescribed drugs for treating attention-deficit hyperactivity disorder. Previous research suggested that MPH is a reinforcer for rats, but not all of the manipulations to show that lever pressing is controlled by the contingency to obtain MPH have been examined. In Experiment 1, responding for MPH on a progressive ratio (PR) schedule was assessed. Rats self-administered varying doses of MPH (0.056-1.0 mg/kg/infusion) on a PR schedule of reinforcement, and self-administered more MPH than saline, with maximal responding occurring at a unit dose of 0.56 mg/kg/infusion. Experiment 2 examined if there were differences in responding between contingent and noncontingent MPH (0.56 mg/kg/infusion) on a fixed ratio schedule of reinforcement. Results showed that rats responded for contingent MPH, and that responding was not maintained when MPH was delivered noncontingently. Experiment 3 examined self-administration of MPH (0.1 or 0.3 mg/kg/infusion) during long access (6 hr) compared to short access sessions (1 hr). Results showed that rats given long access to MPH showed an escalation of intake across sessions, with this escalation being more pronounced at the lower unit dose (0.1 mg/kg/infusion); in contrast, rats given short access to MPH did not show an increase in MPH self-administration across sessions at either MPH dose tested. Taken together, these results indicate that MPH is an effective intravenous reinforcer for rats and that, similar to other stimulants such as cocaine, amphetamine and methamphetamine, MPH is subject to abuse as reflected by dysregulated intake across repeated long access sessions.
Marusich
Julie A
JA
Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY 40636, USA. jmarusich@uky.edu
Beckmann
Joshua S
JS
Gipson
Cassandra D
CD
Bardo
Michael T
MT
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D013997:Time Factors
D000697:Central Nervous System Stimulants; D008774:Methylphenidate