CONDITIONED PLACE PREFERENCES, CONDITIONED LOCOMOTION, AND BEHAVIORALSENSITIZATION OCCUR IN RATS TREATED WITH DIETHYLPROPION

Diethylpropion is a centrally acting appetite-suppressing drug thought to act primarily through catecholamine pathways in the brain. In the present study, four doses of diethylpropion (0, 10, 20, and 40 mg/kg, intraperitoneally) were administered to rats to examine the hypothesis that the drug has psychomotor stimulant properties such as the abilit y to induce conditioned behaviours and behavioural sensitization. The rats were administered drug and then vehicle on alternating days, and confined to a ''drug-'' or vehicle-paired side of a two-compartment bo x for 16 pairings. Only the 10-mg/kg dose of diethylpropion increased spontaneous locomotor activity in comparison to vehicle; the 20- and 4 0-mg/kg doses significantly decreased spontaneous locomotion. All dose s of diethylpropion decreased spontaneous rearing, and the 20-and 40-m g/kg doses produced significantly less rearing than the 10-mg/kg one. At the 10-mg/kg dose, conditioned place preferences, conditioned locom otion, and conditioned rearing were observed. The 40-mg/kg dose produc ed conditioned rearing and conditioned defecation. In response to a 5- mg/kg challenge injection of diethylpropion, behavioural sensitization in locomotion and rearing occurred in rats that had previously receiv ed any one of the three doses of diethylpropion. Over 36 days, decreas ed weight gain was observed only in the 20- and 40-mg/kg groups. The r ats were killed 48 h after the last drug injection, and whole brain wa s analyzed for levels of the catecholamines, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-HT (not a catecholamine), an d 5-hydroxyindoleacetic acid (5-HIAA) by HPLC with electrochemical det ection. No significant differences from control values were found, ind icating that diethylpropion has no long-term effects on levels of thes e brain chemicals. The results support the hypothesis that diethylprop ion has amphetamine-like psychomotor stimulant properties.