Evaluation of the reinforcing effects of monoamine reuptake inhibitors under a concurrent schedule of food and i.v. drug delivery in rhesus monkeys.

Full Abstract

Most medications prescribed for attention-deficit-hyperactivity disorder are psychomotor stimulants with reinforcing effects in laboratory animals (eg methylphenidate). The present studies were conducted to evaluate the reinforcing effects of the recently approved medication atomoxetine in monkeys trained to 'choose' between automated deliveries of either an i.v. injection or food. Rhesus monkeys were trained to lever-press under concurrent schedules of reinforcement; responses on one lever resulted in an injection of either saline or drug, and responses on the alternative lever resulted in food delivery. Data were collected on four measures: response rates, percentage of total responses occurring on the injection-lever (% ILR), number of injections earned, and number of food pellets earned. Dose-effect functions were determined for cocaine (0.003-0.3 mg/kg/inj), methylphenidate (0.003-0.1 mg/kg/inj), amphetamine (0.003-0.1 mg/kg/inj), atomoxetine (0.01-0.3 mg/kg/inj), and desipramine (0.03-1.0 mg/kg/inj) using a double alternation schedule of saline and drug availability. Results indicate that the distribution of behavior changed according to the drug and dose available for self-injection. Saline availability was typically associated with high rates of food-maintained responding. The % ILR increased from 3+/-1% when saline was available to >90% when >0.03 mg/kg/inj of cocaine, methylphenidate or d-amphetamine was available. However, no dose of atomoxetine or desipramine maintained self-administration behavior on the injection-lever. The number of food pellets earned per session decreased as the dose of each drug increased, indicative of behavioral activity with all five drugs. The reinforcing effects of cocaine, methylphenidate, and d-amphetamine in these studies are consistent with previous findings in nonhuman primates and with their documented abuse liability. The absence of reinforcing effects of atomoxetine support the view that, like desipramine, it has no evident abuse potential.

Author information

Author/s: Gasior, Maciej (M); Bergman, Jack (J); Kallman, Mary Jeanne (MJ); Paronis, Carol A (CA);

Affiliation: McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.

Grants: DA03774 (Agency:NIDA NIH HHS) ; DA10566 (Agency:NIDA NIH HHS) ; DA11453 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology), published in United States. (Language: eng)

Reference: 2005-Apr; vol 30 (issue 4) : pp 758-64

Dates: Created 2005/03/18; Completed 2005/07/28; Revised 2007/11/14;

PMID: 15526000, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adrenergic Uptake Inhibitors - adverse effects
Animals
Attention Deficit Disorder with Hyperactivity - drug therapy; metabolism; physiopathology
Brain - drug effects; metabolism; physiopathology
Central Nervous System Stimulants - adverse effects
Cocaine - adverse effects
Desipramine - adverse effects
Dextroamphetamine - adverse effects
Disease Models, Animal
Dose-Response Relationship, Drug

Associated Chemicals: Adrenergic Uptake Inhibitors (0) ; Central Nervous System Stimulants (0) ; Propylamines (0) ; Methylphenidate (113-45-1) ; Cocaine (50-36-2) ; Desipramine (50-47-5) ; Dextroamphetamine (51-64-9) ; atomoxetine (83015-26-3)

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